Displaying One Session

On-Demand e-Poster Display Poster Display
Date
20.11.2020
Time
09:00 - 20:00
Location
On-Demand e-Poster Display
e-Poster Display Session (ID 87) Poster Display

Breast cancer, early stage (ID 1141)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

7P - Machine learning intratumoral and axillary lymph node magnetic resonance imaging radiomics for predicting axillary lymph node metastasis in patients with early-stage invasive breast cancer (RBC-01 Study) (ID 991)

Presentation Number
7P
Lecture Time
09:00 - 09:00
Speakers
  • Yujie Tan (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In current clinical practice, the routine approaches of axillary lymph node (ALN) status evaluation through sentinel lymph node biopsy (SLNB) is unsatisfied with high false-negative rate and brings significant complications. We aimed to develop a preoperative magnetic resonance imaging radiomic-based signature for predicting ALN metastasis (ALNM) in a non-invasive way.

Methods

A total of 1,090 early-stage invasive breast cancer patients from 4 institutions were enrolled in this multicenter, retrospective, diagnositc study. Radiomic signature for ALNM prediction were constructed by machine learning in 803 patients from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (Training cohort). The clinical-radiomic siganture was constructed by combining radiomic signature and significant clinic-pathological risk factors and was validated in patients from prospective phase III trials [NCT01503905] (Internal validation cohort, n=106), and Shunde Hospital and Tungwah Hospital (External validation cohort, n=181). This study is registered with ClinicalTrials.gov (NCT04003558) and Chinese Clinical Trail Registry (ChiCTR1900024020).

Results

The radiomic signature for predicting ALNM consisted of intratumoral and ALN features showed AUCs of 0.91, 0.88, and 0.85 in the training, internal validation and external validation cohorts. The clinical-radiomic signature achieved the highest AUCs of 0.93, 0.91, and 0.91 in the training, internal validation and external validation cohorts, which successfully discriminate high- from low risk relapse patients (HR 0.12, 95% CI 0.03–0.53; P<0.001) and was similar to the performance in ALNM and non-ALNM (HR 0.28, 95% CI 0.09–0.87; P=0.002). In additon, the clinical-radiomic signature also performed well in the subgroup of N1, N2, N3 status (AUCs of 0.89, 0.90, 0.97).

Conclusions

This study developed a clinical-radiomic signature incorporated the intratumoral and ALN radiomic features and clinical risk factors, which could serve as a non-invasive tool to evaluate ALN status for guiding surgery plans of early-stage breast cancer patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

8P - Knowledge, practice and attitudes of physicians in low- and middle-income countries (LMIC) on fertility and pregnancy-related issues in young breast cancer patients (ID 781)

Presentation Number
8P
Lecture Time
09:00 - 09:00
Speakers
  • Shah Zeb Khan (Bannu, Pakistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Fertility and pregnancy-related issues are a priority area of concern for young breast cancer (BC) patients (pts). Limited evidence exists on knowledge, practice and attitudes of physicians practicingin low- and middle-income countries (LMIC)towards these issues.

Methods

A 19-item questionnaire adapted from an international survey (Lambertini et al, Breast 2018) exploring issuesaboutfertility preservation and pregnancy after BCwas sent by email to physicians from LMIC involved in BC care.Descriptive analyses were performed.

Results

A total of 288 physicians completed the survey. Median age was 38 years (interquartile range 33-45).Respondents from Asia, Africa, America and Europe filled in the survey: the 3 most represented countries were Mexico (27.1%), India (18.4%) and Brazil (8.3%).The majority of respondents were medical oncologists (44.4%)working in an academic setting (46.9%). Among respondents, 40.2% and 53.8% reported never having consulted the available international guidelines on fertility preservation and pregnancy after BC, respectively. 25.0%, 19.1% and 24.3% of respondents declared to be not at all knowledgeable about embryo, oocyte or ovarian tissue cryopreservation, respectively. 29.2%, 23.6% and 31.3% declared that embryo, oocyte and ovarian tissue cryopreservation are not available in their countries, respectively. 57.6% of respondents disagreed or were neutral on the statement that controlled ovarian stimulation (COS) can be considered safe in BC pts; 29.9%suggested that COS should not be considered safe in pts with hormone receptor-positive (HR+) disease. 49.7% and 58.6% of respondents agreed or were neutral on the statement that pregnancy in BC survivors may increase the risk of recurrence overall or only in those with HR+ disease, respectively. In contrast, 49.0% agreed that COS in BC survivors can be safely considered.

Conclusions

Several misconceptions exist among physicians from LMIC on fertility and pregnancy-related issues in young BC pts. Increased awareness and further educational initiatives are needed to improve adherence to available guidelines and pts’oncofertility counseling.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.F. Ponde: Advisory/Consultancy: Lilly; Honoraria (self): Roche,Novartis, AstraZeneca and Lilly. M. Brandão: Honoraria (self), Travel/Accommodation/Expenses: Roche/GNE. I.B. Spasojevic: Advisory/Consultancy: Roche, Novartis, Amicus; Honoraria (self): Roche, Novartis, Pfizer, AstraZeneca. A. Odhiambo: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Roche, Novartis; Advisory/Consultancy: Pfizer, AstraZeneca, Janssen. M. Tagliamento: Travel/Accommodation/Expenses: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda; Full/Part-time employment, Medical Writer: Novartis, Amgen. M. Lambertini: Advisory/Consultancy: Roche, Novartis; Honoraria (self): Roche, Takeda, Theramex, Novartis, Pfizer, Lilly. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

9P - Survival status of elderly women with HR+ early breast cancer: An analysis of SEER database (ID 430)

Presentation Number
9P
Lecture Time
09:00 - 09:00
Speakers
  • Wang Hao (Chengdu, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Women with HR+(ER and/or PR positive) in early breast cancer usually have a better outcome than other cancer variants. However, as the patient age, there were few reports on the survival status of elderly women in HR+ early breast cancer and concomitant diseases. Base on a large-scale population, the results of statistical analysis would aid in clinical decisions and effective interventions on the treatment of elderly patients.

Methods

Based on the Surveillance, Epidemiology, and End Results (SEER) database, elderly (age≥60) female patients diagnosed HR+ early breast cancer from 2010 to 2016 were included. They were divided into two groups: elderly patients (age 60-74, group A) and senior elderly patients (age≥75, group B). Kaplan-Meier survival analysis was used to compare the 5-year overall survival (OS) rate, cumulative mortality, and the proportion cause of death.

Results

In total there were 147,969 cases were included, which were 100,091 cases in group A and 47,878 cases in group B. The 5-year OS in group A and B were 89.9% vs. 68.8% (HR 3.53, 95% CI 3.43-3.64, P < 0.001) respectively. The proportion of HER2- and HER2+ cases in group A were 90.2% and 9.8%, which 5-year OS were 90.2% vs. 87.7% (HR 0.77, 95% CI 0.72-0.83, P < 0.001). The proportion of HER2- and HER2+ cases in group B were 91.9% and 8.1%, which 5-year OS were 69.5% vs. 61.0% (HR 0.70, 95%CI 0.66-0.75, P < 0.001). There was no significant difference in cumulative mortality between breast and non-breast cancer related deaths (HR: 0.98, 95% CI 0.93-1.03, P = 0.4) in group A; but that was significantly difference in group B (HR: 0.77, 95% CI 0.733-0.799, P < 0.001). The primary non-breast related death in group A were diseases of the heart (12.1%), COPD and related conditions (4.8%); while in group B that were diseases of the heart (20.43%) and cerebrovascular disease (5.4%).

Conclusions

The risk of death in elderly HR+ early breast cancer patients was relatively increasing with age, especially the death caused by cardiovascular and cerebrovascular events. HR+/HER2+ patients have a higher risk of death requiring further intensive treatment. The age-related comorbidity risk and breast cancer subtypes should be considered in the treatment of these patients to make a comprehensive treatment decision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

10P - Neoadjuvant immunotherapy plus chemotherapy in early triple-negative breast cancer: A meta-analysis of randomized controlled trials (ID 531)

Presentation Number
10P
Lecture Time
09:00 - 09:00
Speakers
  • Jessa Gilda P. Pandy (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In the early stages, the use of neo-adjuvant systemic treatment is the standard of care in TNBCs. Patients who achieve a pathological complete response (pCR) have improved survival outcomes. The programmed cell death receptor ligand, PD-L1, has been shown to have high expression in TNBCs. To date, major research efforts are being undertaken to determine the applicability of PD-1/PD-L1 immune checkpoint inhibitors in TNBC.

Methods

A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were utilized to identify RCTs investigating the use of neoadjuvant PD-1/PD-L1 inhibitors plus standard chemotherapy in TNBC. Trials that were published up to March 2020 were included and were appraised. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) were calculated for pCR. Subgroup analysis of pCR rates based on PD-L1 expression was also done.

Results

Four RCTs were included (N=384). The addition of immunotherapy to chemotherapy in the neo-adjuvant setting showed significant pCR benefit of 58.5% vs 42.2% compared to chemotherapy alone (OR 1.76, 95% CI 1.11-2.79, P <0.02). Subgroup analysis based on PD-L1 expression showed that in the immunotherapy plus chemotherapy group, there is a significantly higher pCR rate in the PD-L1-positive population than in the PD-L1 negative group (64.5% vs 39.4%). The addition of immunotherapy showed a significant benefit in improving pCR in the PD-L1-positive group (OR 1.55, 95%CI 1.16-2.09, p = 0.003, I2 =0%).

Conclusions

The addition of PD-1/PD-L1 inhibitors to standard chemotherapy is associated with increased pCR rates in patients with TNBC, hence, supporting its use for patients in the neo-adjuvant setting. Subgroup analysis showed that the benefit of adding immunotherapy was more significant in those with PD-L1-expressing tumors. This result indicates that the PD-L1 immune marker may have utility in selecting TNBC patients who can benefit more from PD-L1 inhibitors. Longer follow-up and further analysis of these studies would hopefully demonstrate significance in other outcomes such as progression-free survival and overall survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

11P - Genetically predicted bipolar disorder is causally associated with increased risk of breast cancer: A Mendelian randomization analysis (ID 683)

Presentation Number
11P
Lecture Time
09:00 - 09:00
Speakers
  • Haoxin Peng (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Epidemiologic findings suggested that bipolar disorder (BD) may be associated with increased risk of breast cancer. However, there are few studies that comprehensively evaluate their correlation and the causal effect remains unknown. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.

Methods

Utilizing 6 BD-related single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association studies, we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122 977 cases and 105 974 controls. Study-specific estimates were summarized using inverse-variance-weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical type of breast cancer were also conducted.

Results

MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR = 1.058; 95% CI 1.023-1.093, p < 0.001). When results were examined by immunohistochemical type, a strong association was observed between genetically predicted BD and estrogen receptor-positive (ER) breast cancer (OR = 1.048, 95%CI 1.008-1.090 p = 0.0177) rather than ER-negative breast cancer (OR = 1.026, 95%CI 0.975-1.081 p = 0.3231). Additionally, the results demonstrated the absence of the horizontal pleiotropy.

Mendelian randomization estimates of the associations between bipolar disorder and risk of breast cancer overall and immunohistochemical types

Outcome IVW method MR-Egger Weighted median method
OR (95% CI) P-value OR (95% CI) P-value OR (95% CI) P-value
Breast cancer overall 1.058 (1.023, 1.093) 0.0009 1.032 (0.969, 1.099) 0.3858 1.044 (1.006, 1.083) 0.0239
ER-positive breast cancer 1.048 (1.008, 1.090) 0.0177 1.004 (0.942, 1.070) 0.9118 1.030 (0.998, 1.074) 0.1622
ER-negative breast cancer 1.026 (0.975, 1.081) 0.3231 1.085 (0.986, 1.195) 0.1713 1.041 (0.978, 1.109) 0.2063

Conclusions

Our findings provide evidence for a causal relationship between genetically predicted BD and increased breast cancer risk, overall and among specific immunohistochemical type. Further studies are warranted to investigate the underlying mechanism.

Legal entity responsible for the study

Haoxin Peng.

Funding

China National Science Foundation (Grant No. 81871893); Key Project of Guangzhou Scientific Research Project (Grant No. 201804020030); Cultivation of Guangdong College Students' Scientific and Technological Innovation (“Climbing Program” Special Funds) (Grant No. pdjh2020a0480).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

12P - Stromal tumour-infiltrating lymphocytes in human epidermal growth factor receptor 2-overexpressing breast cancer: Association with negative nodal metastasis (ID 804)

Presentation Number
12P
Lecture Time
09:00 - 09:00
Speakers
  • Ren Xiaoqiu (Hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The tumor-infiltrating lymphocytes (TILs), especially stromal TILs, have showed a prognostic role in human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer. Stromal TILs are associated with higher pathological complete remission (pCR) rates after neoadjuvant chemotherapy. However, the relation between stromal TILs in primary breast cancer and axillary nodal metastasis remains uncertain.

Methods

A retrospective review of pathological reports of 763 patients with breast infiltrating ductal carcinoma (IDC) was conducted. The gene expression and clinical data of 662 IDC cases were downloaded from the TCGA database. In silico analysis was based on the gene expression data. The “Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data” (ESTIMATE) algorithm was used to calculate the stromal and immune scores in N0 and N+ cases.

Results

In HER2+ breast cancer, the fractions of stromal TILs are higher than 30% (37.57% versus 19.67%, P=0.01) and 40% (25.97% vs 8.20%, P=0.003) in lymph node negative cases comparing to nodal metastasis cases. The fractions of stromal TILs in HER2- breast cancer showed no difference between N0 and N+ stage cases. We further compare the fractions of stromal TILs between N0 and N+ cases in different subtypes of breast cancer cases. The stromal TILs (%) is only higher in primary tumors of N0 HER2 amplified breast cancer cases than N+ cases (P=0.014). The stromal TILs (%) of primary tumors are similar between N0 and N+ cases in Luminal A (hormone receptor (HR)+/HER2-) (P=0.261), Luminal B (HR+/HER2+) (P=0.838) and triple negative (HR-/HER2-) subtypes (P=0.456). The primary tumors immune scores of N0 and N+ cases show no significantly difference in HER2+/- breast cancer. The stromal scores of N+ cases are higher than N0 cases in HER2+ breast cancer (P=0.015). The stromal scores are similar between N0 and N+ cases in HER2- breast cancer.

Stromal TILs(%) N0(cases) % N+(cases) % P value
Her2+ 0-9 72 39.78 28 45.90
10- 109 60.22 33 54.10
0.401
0-19 101 55.80 40 65.57
20- 80 44.75 21 34.43
0.181
0-29 113 62.43 49 80.33
30- 68 37.57 12 19.67
0.01
0-39 134 74.03 56 91.8
40- 47 25.97 5 8.2
0.003
Stromal TILs(%) N0(cases) % N+(cases) % P value
Her2+ 0-9 219 59.03 83 55.70
10- 152 40.97 66 44.30
0.487
0-19 286 77.09 115 77.18
20- 85 22.91 34 22.82
0.982
0-29 313 84.37 124 83.22
30- 58 15.63 25 16.78
0.747
0-39 335 90.30 135 90.60
40- 36 9.70 14 9.4
0.914

Conclusions

The higher fraction of stromal TILs is negatively related to lymph nodes metastasis in her2-positive breast cancer. Since the stromal fraction of tumor tissue may be higher in HER2+ N+ breast cancer, it also tends to be associated with nodal metastasis. In total, it is not the absolute quantity of immune cells, but the relative quantity of TILs in tumor stroma (which we evaluated as stromal TILs (%)) makes a vital role in predicting nodal stage of HER2 amplified IDC.

Legal entity responsible for the study

Weiqichun.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

13P - A retrospective observational study on neoadjuvant chemotherapy in older adults based on the Joint Breast Cancer Registry Singapore (ID 627)

Presentation Number
13P
Lecture Time
09:00 - 09:00
Speakers
  • Johan Chan (Singapore, SA, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

According to the SEER cancer statistics from 2013 to 2017, 43.4% of all newly breast cancers are diagnosed in women aged 65 years and older. Despite a relatively high prevalence of older adults with newly diagnosed breast cancer, elderly patients are often under-represented in the pivotal neoadjuvant trials. Recommendations for treatment with neoadjuvant chemotherapy (NAC) are based on subgroup analyses and extrapolation of study results from younger patients.

Methods

This retrospective observational study collected data from the Joint Breast Cancer Registry (JBCR) on older adults aged ≥ 65 years treated with NAC for breast cancer at the National Cancer Centre Singapore from October 2014 to October 2019. Patients in the JBCR had detailed clinical and pathological information including hormone receptor (HR), HER2 status, type of NAC. Outcomes and adverse events were retrieved from electronic medical records. Pathological complete response(pCR) was defined by the absence of residual disease in the breast and lymph nodes following NAC.

Results

Of 353 patients who underwent NAC, 66(18%) patients were older adults aged ≥ 65 years. Patients characteristics are decribed in the table. The median age was 69 (65-83) years. 31(46%) patients had HER2+ disease. 13(19%) were triple negative breast cancer (TNBC). 18(27%) patients were unable to complete NAC, of which 10(15%) were due to side effects while 5 (7.5%) had progressive disease during treatment and the remainder 3(5%) refused the planned treatment. Half of the cohort with HER2+ disease had anthracycline/taxane based chemotherapy along with HER2 directed therapy of either trastuzumab or the combination trastuzumab and pertuzumab. 13 (19%) patients had pCR, 11 were HER2+ while 1 was HR+/HER 2- and the other was TNBC.

Patient characteristics

No. (%)
Breast cancer diagnosis that are 65 years and above 66 (18)
median age (Range) 69 (65-83)
median ECOG(range) 0 (0-2)
Clinical T Staging
2 14 (21)
3 to 4 52 (79)
Clinical N Staging
0 14 (20)
1 to 3 51 (79)
nX 1
HR status
Negative 25(37)
Positive 41(63)
Human epidermal growth factor receptor 2 (HER2)
Negative 35 (54)
Positive 31 (46)
Histology
HR+ /HER2- 22 (33)
HR +/ HER2+ 19 (28)
HR - / HER2+ 12 (18)
Triple negativeTNBC (HR- /& HER2-) 13 (18)
NACcompleted/ NAC not completed 48(72) / 18 (27)
IncompletionReason
PD 5(27)
Side effects 10(55)
Refused treatment 3 (16)
Pathological Complete Response
Overall 13(18)
TNBC 1
Her2+ 11(17)
ER +/ HER2- 1

Conclusions

We report a cohort of older adults who had undergone NAC at our centre. Consistent with existing studies, 72 % of the patients completed NAC. In keeping with data on younger patients, older adults with HER2+ breast cancer had higher pCR. However, unlike younger women with TNBC, older adults in this study had lower rates of pCR which was also noted in a recent pooled analysis. This could reflect a heterogeneity of TNBC in older women which warrants further investigations in the future

Legal entity responsible for the study

CIRB Singhealth 2019/093/A.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

14P - BRCA mutation and clinical outcomes in breast cancer focusing on survivals and failure patterns: A long-term follow-up study of Koreans (ID 353)

Presentation Number
14P
Lecture Time
09:00 - 09:00
Speakers
  • Hakyoung Kim (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The purpose of this study was to evaluate the effect of BRCA mutation on survival and recurrence rate, focusing on risk of ipsilateral recurrence and contralateral breast cancer in breast cancer patients who underwent genetic screening for BRCA1/2 mutation and were treated at Samsung Medical Center.

Methods

We retrospectively reviewed medical records of 300 patients with breast cancer who underwent genetic screening for BRCA1/2 genes and were treated at Samsung Medical Center between January 1, 2000 and December 31, 2010. Ultimately, clinical outcomes of 273 patients were analyzed.

Results

The median follow-up duration was 102 months (range, 1 to 220 months). BRCA1/2-mutated tumors had shorter 10-year disease-free survival (DFS) rate compared to those with non-mutated tumors (62.8% vs. 80.0%, p = 0.02). Regarding failure patterns, BRCA1/2-mutated tumors showed higher incidence of contralateral breast cancer than non-mutated tumors (BRCA1/2 non-mutated vs. mutated tumors: 4.9% vs. 26.0%, p < 0.001). BRCA mutation status remained a significant prognostic factor for contralateral breast recurrence-free survival (HR: 4.155, 95% CI: 1.789-9.652; p = 0.001).

Conclusions

Korean patients having BRCA mutation showed inferior DFS compared to those without BRCA mutation. BRCA mutation status is a strong predictor of recurrence in contralateral breast. Strategies such as prophylactic treatment and active surveillance should be discussed with breast cancer patients who have BRCA mutations.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

15P - Designing of multimodal targeted tumor-seeking nanomedicine for triple-therapeutic effect (ID 156)

Presentation Number
15P
Lecture Time
09:00 - 09:00
Speakers
  • Vellingiri Yasothamani (Coimbatore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is a major ongoing health problem among women in both developing and developed countries. Her2/neu positive is the subtype of breast cancer. We tested an integrated innovatively designed new tumour-seeking nanomedicine (TSN) for high therapeutics antitumor effect on advanced breast cancer that overexpressed the Her2/neu receptor.

Methods

Herein, we designed the special photodynamic molecule porphyrin combined with the anticancer drug doxorubicin (DOX), enabling it to target cancer biomarkers and measuring the singlet oxygen production with thermal heat to archive extraordinary selective PDT/PTT/Chemotherapy in vitro. The tumor-seeking nanomedicine (TSN) targets the triple therapeutic effect of breast cancer. Furthermore, in vivo phototherapy and chemotherapy using targeted nanoparticles in mice models were also done.

Results

Encouragingly, multimodal targeted TSN shows selective Her2/neu receptor-mediated response in breast cancer, incinerates the tumor treated under NIR irradiation triggering the porphyrin and DOX co-release and enhancing the distribution of DOX in nuclei; the released porphyrin molecules also function as multiphase that can efficiently convert NIR-light to heat inside tumor cells for PTT, and again NIR-light to singlet oxygen for PDT. Due to these unique properties, TSN had excellent antitumor effects under NIR irradiation. The excellent role of TSN based triple-targeted therapy produced the best anticancer response to trigger the tumor cell death and was effective to protect the mice from cancer relapse.

Conclusions

Conjugation of porphyrin and DOX for the evaluation of such complexes in phototherapy in Her2/neu target human cancer cells. This multi-model therapy approach will make it much more effective to overcome tumors than a single therapeutic approach. TSN exhibited high selectivity and efficient tumor inhibition in-vivo without affecting the normal tissues. Therefore the clinical translation of our TSN and the proposed way might be realistic and the integrated components of TSN have been approved by the US FDA for human clinical usage. Therefore, integrated TSN achieved unprecedented selectivity and shows highly versatile next-generation clinical translation for advanced nanomedicine against cancers.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

16P - Topical henna cream in prevention of radiation-induced dermatitis in breast cancer: A randomized double-blind clinical trial (ID 983)

Presentation Number
16P
Lecture Time
09:00 - 09:00
Speakers
  • Mansour Lesan (Tehran, Iran)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Radiotherapy plays an important role in the treatment of cases who had breast conserving surgery. Breast cancer patients who receive radiotherapy develop acute skin complications which are known as radiation dermatitis (RD) during radiotherapy or shortly after it. Radiation dermatitis is one of the most common side effects. It affects approximately 95% of patients. This complication has a profound effect on patients' quality of life due to pain and discomfort and can reduce tolerance to treatment and in some cases discontinuation or delay of radiotherapy. This can effect disease control in the long term. So, prevention and treatment of RD is important for health care providers and it is essential to produce effective health products to prevent and treat this disease. Henna (Lawsonia inermis L.) is a medicinal plant which has antimicrobial, anti-inflammatory, and skin-enhancing properties, all of which are useful for people who have radition dermatitis. Also, studies have shown antimicrobial, anti-inflammatory, analgesic, and wound healing effects of henna. This research aimed to evaluate the efficacy of a topical henna preparation (HP) in preventing and reducing the severity of RD in breast cancer patients.

Methods

This was a prospective double-blind clinical study which contained 43 breast cancer patients aged 18-75 years who had breast-conserving surgery and were going to receive radiotherapy. They were randomly allocated into two groups, those who received the topical HP or those who received placebo, twice daily for six weeks, from the first day of treatment. Grade of dermatitis was evaluated weekly based on RTOG grading system.

Results

The present study showed that HP could reduce the severity of RD. The use of HP delayed the onset of grade 2 RD for two weeks, also, it delayed the onset of grade 3 RD for one week compared to the placebo group. At the end of the sixth week, in the patients who received the HP, the grade 2 RD (20% vs. 56.52%) as well as grade 3 RD (10% vs. 26.09%) significantly decreased (p=0.004).

Conclusions

Topical henna cream is an inexpensive and accessible herbal medicine that can be effective in preventing and reducing the severity of RD in patients with breast cancer.

Clinical trial identification

IRCT2019110704537N1.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

17P - Comparison of dose distribution in the postoperative breast cancer patients irradiated with the technique of deep inspiratory breath hold and dynamic techniques (ID 148)

Presentation Number
17P
Lecture Time
09:00 - 09:00
Speakers
  • Ewa B. Telka (Gliwice, Poland)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is the most common cancer in women in Poland. In patients with cancer located on the left side, breast radiotherapy is associated with the irradiation of part of the heart. It was calculated that for every 1 Gy dose of radiation deposited in the heart, the risk of heart complications increases by 7.4%.

Methods

The subject of analysis was a group of 50 patients treated in the National Institute of Oncology, Department of Radiotherapy, Gliwice from June 2018 to December 2019. The age of patients ranged from 30 to 70 (median 63 years). All patients were after surgeries (38 patients after BCT with SNB and 12 patients after left breast amputation). All patients were additionally irradiated using Deep Inspiratory Breath Hold technique. Dose distributions per heart and lungs were compared in IMRT, Rapid Arc, and DIBH techniques. Radiation complications from the skin were assessed according to WHO scale.

Results

In all irradiated patients the dose distribution in the technique on suspended inhalation was better compared to the dynamic IMRT and Rapid Arc techniques, with dose reduction per heart by about 10-15% and per lung from 5 to 10%. No higher than II degree of acute and late skin reaction in the DIBH technique was observed in comparison with dynamic techniques.

Conclusions

1) Deep Inspiratory Breath Hold technique is a simple non-invasive method which effectively reduces the dose of radiation absorbed by the heart muscle. 2) Irradiation of patients with deep inspiratory allows a reduction of the lungs dose by about 5-10 %. 3) The technique of irradiation of patients during deep inspiratory is a simple, non-invasive method of treatment of patients reducing the risk of radiation complications from the heart and the lungs in comparison with dynamic, IMRT, and Rapid Arc techniques.

Legal entity responsible for the study

The authors” without further recourse to the authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

18P - A prospective randomized study comparing cosmetic outcome of sequential electron boost versus simultaneous integrated boost with IMRT to lumpectomy cavity during adjuvant radiotherapy to breast following BCS in carcinoma breast in Indian patients (ID 595)

Presentation Number
18P
Lecture Time
09:00 - 09:00
Speakers
  • Sravya Bommera (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Compared to sequential conventional fractionation schedule, Simultaneous integrated Boost provides increased dose homogeneity, with less unintended excessive dose outside the boost area; in combination with a higher dose per fraction to the tumour bed, resulting in a shorter overall treatment time spanning over 5 1⁄2 weeks. We compared cosmesis using the Harvard cosmesis scale and dosimetry of SIB IMRT versus sequential electron boost in breast cancer patients.

Methods

Patients in our Institute who have undergone breast-conserving surgery and received adjuvant chemotherapy, who are referred for adjuvant radiotherapy. The study period spanned from 1st May 2016 to 31st March 2018.

Results

The baseline Harvard score for grading breast cosmesis in both the arms was excellent (84% in SIB and 81% in SEB) or good(16% in SIB and 19% in SEB). None of the patients in either arm had fair or poor cosmesis. Assessment of cosmesis at the end of radiation therapy showed a dip from excellent to good and fair in both the arms ( 34% versus 9% with excellent cosmesis, 53% versus 72% with good cosmesis and 13% versus 19% with poor cosmesis in SIB versus SEB arms) but the patients in the SEB arm had comparatively much lower cosmetic score. However, this difference was not statistically significant(p=0.045). Overall cosmesis at the end of 3 months was better in SIB arm compared to that of the SEB arm and was statistically significant (93% with excellent and good cosmesis in SIB vs 65% in SEB p<0.001). At 6 months of follow-up in SIB arm, there was an improvement of the cosmesis with a majority of the patients showing excellent(59%) and good (34%) cosmetic score.

Conclusions

In a selected cohort of patients who have undergone breast conservation surgery, a simultaneous integrated boost along with WBI is considered equivalent radiobiological to sequential electron boost after WBI. This study reports better cosmetic outcomes and favourable toxicity profile with SIB compared to SEB over short-term follow-up which is statistically significant.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

19P - Musculoskeletal pain and health-related quality of life among breast cancer patients (ID 234)

Presentation Number
19P
Lecture Time
09:00 - 09:00
Speakers
  • Aslin S. Valiyagath (Thrissur, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The musculoskeletal pain is one of the leading health problems among women. This study aims to examine the associations between musculoskeletal pain and health-related quality of life (HR-QOL) among breast cancer patients and women without a history of breast cancer.

Methods

A cross-sectional study was conducted among 68 breast cancer patients for an average of 3.5 years and 137 postmenopausal women without a history of cancer. Musculoskeletal pain was assessed using a 10-cm visual analog scale; HR-QOL was examined using the Medical Outcomes Study Short Form (SF-36) health survey. Linear regression was used to estimate the associations between pain and HR-QOL in both groups.

Results

Approximately 64 % of the breast cancer patients andwomen in the comparison group reported musculoskeletal pain.Among women with breast cancer, those with pain had significantlylower HR-QOL scores in the physical (52.2 vs. 42.6;p<0.001) and mental (52.7 vs. 45.5; p=0.01) component summary scores compared with those without pain. In the comparisongroup, pain was associated with significantly lower scores in the physical (55.4 vs. 46.0; p<0.001), but not the mental, component summary score (52.1 vs. 52.4; p=0.82). The significantassociations between pain and HR-QOL persisted afterconfounder adjustment in both groups. Among women withsimilar severity of pain, breast cancer patients reported significantlylower HR-QOL in the mental summary component compared with the women in the comparison group.

Conclusions

Among breast cancer patients, musculoskeletal pain adversely affects both mental and physical components of HR-QOL. Preventing or treating musculoskeletal pain may improve overall HR-QOL among breast cancer patients.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

20P - Molecular parallelisms and divergences between human and canine cancers (ID 347)

Presentation Number
20P
Lecture Time
09:00 - 09:00
Speakers
  • Sadaf Ambreen (, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tumorigenesis has been widely accepted as an evolutionary process that comprises two stages of evolution between tumors and normal tissues (Stage I) and within tumors (Stage II) 1. Patterns of mutation and natural selection, the predominant evolutionary driver forces, vary at the two stages based on the evidence of low genetic convergence among different cancer cases revealed by The Cancer Genome Atlas (TCGA) data and of extremely high intra-tumor genetic diversity measured in high-density sampling studies (Ling et al. 2015; Sottoriva et al. 2015). At Stage, I, positive and negative selection may both exist but neatly counteract in absence of recombination, presenting a plausible neutrality 1, whereas non-Darwinian (neutral) selection was increasingly supported at Stage II by the high-density sampling studies and comparatively genomic and transcriptional distances among distinct normal and cancerous cell populations. Deciphering the evolutionary patterns during tumorigenesis such as selectivity or neutrality, adaptive convergence, or divergence is of both theoretical and clinical significance. Cross-species cancer genomics, independent evolution from normal tissues, provide an excellent opportunity to address this long-standing issue: Does selection drive cancer evolution along with a relatively deterministic (selectivity) or contingent (neutrality) way across species?

Methods

GATAK pipeline and Mutect2.

Results

We performed whole-genome sequencing analysis by using GATAK pipeline and Mutect2 for twenty-four dog mammary cancers and identified 47715 somatic mutations comprising 210 exonic mutations. Comparison between human and dog reveals similarities and differences in the mutation profiles across both species, in terms of the mutated driver genes and mutation number, which are likely to influence tumor behavior and response to treatments. Human breast cancer had a higher median mutation burden comparable to canine mammary cancer, in exonic regions (2.67 and 0.187 average no. of mutations per tumor per megabase (Mb), respectively).

Conclusions

Taken together, for the first time, we reported canine mammary tumors comprising mutated genes, mutation burden, mutational patterns, spectrums, and signatures at the whole genome level.

Legal entity responsible for the study

The author.

Funding

CAS-TWAS.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

21P - Neoadjuvant trastuzumab and pertuzumab in real-world data population in two medical institutions in Portugal (ID 988)

Presentation Number
21P
Lecture Time
09:00 - 09:00
Speakers
  • Isabel C. Gomes Fernandes (Barreiro, Portugal)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Neoadjuvant treatment (NAT) refers to the treatment that is administered before surgery for the treatment of cancer. For the last few years the medical community noticed that achieving complete pathological response (pCR), for HER2+ breast cancer patients, after the NAT equates to a long-term surrogate point, which has pushed for the development of treatment strategies based of neoadjuvant use of trastuzumab and pertuzumab. We implemented an institutional protocol in 2018 to treat HER2+ breast cancer patients that had tumours larger than 2cm and/or axillary disease that had had included anthracyclins, taxanes, trastuzumab and pertuzumab on their NAT regimen. The main goal was to prospectively analyse the effect of this neoadjuvant regimen on pCR (ypT0/is, ypN0/is), as well as on how often does NAT help with breast conservation.

Methods

This non-randomized prospective study was performed in two medical oncology departments in Portugal. It included HER2+ breast cancer patients that had tumours larger than 2cm and/or axillary disease that have been being treated since 2018. These patients were put on the following treatment scheme: 4 cycles of doxorrubicin and cyclofosfamid, followed by 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles.

Results

A total of 38 patients were included in the study. The median age: 54 years; 17 patients had stage II cancer and 21 patients stage III. 26 patients had a ki67 >20%. pCR was achieved in 60,5% of the patients, 58,6 % in the hormonal receptor (HR) positive subgroup and 66,7% in HR-negative patients. 57,9% of the patients received breast conservative surgery and 65,9% received axillary dissection. Only one patient didn’t complete the protocol by own choice and no cardiac toxicity was detected on any patient.

Conclusions

Our results are consistent with those published in previous studies in terms of pCR rate and toxicity, however there was a high number of axillar dissections and for that reason we are working in an institutional protocol for the management of the axillary disease after NAT. Long term follow up is necessary to understand the real impact of pCR and to search for predictive indicators of the response to NAT.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

22P - Correlation of muscle strength and quality of life in Indonesian breast cancer patients who underwent chemotherapy (ID 742)

Presentation Number
22P
Lecture Time
09:00 - 09:00
Speakers
  • Devina A. Halim (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotoxicity may cause sarcopenia, representing a loss of muscle strength and mass, which reduces quality of life (QoL) and physical function. Most of the breast cancer patients underwent chemotherapy reported significant aftereffects. However, the evaluation of muscle strength and QoL were still limited. Hereby, the study aims to evaluate the correlation between muscle strength and QoL in Indonesian breast cancer patients.

Methods

Participants were breast cancer women who underwent chemotherapy. Muscle strength was measured with a JAMAR handgrip. Breast cancer patients were evaluated their QoL from global health status and functional status which compromises the physical functioning (PF), role functioning (RF), emotional functioning (EF), cognitive functioning (CF) social functioning (SF). Assessment was done using the EORTC QLQ-C30. The correlation was analyzed with Pearson and Spearman correlation test.

Results

A population of 80 breast cancer women was involved, with a mean age of 47.39±7.0, median BMI of 23.15 (7.86-47.26) kg/m2 and median muscle strength of 16.5 (3-29) kg. The majority of the patients were stage 2 on diagnosis (76.3%). Median score for each domains were as followed, global health status=66.67(0-100); PF=93.33(0-133.33); RF=100(0-133.33); EF=83.33(33.33-100); CF=100(16.67-100); and SF=100(0-100). Correlations were found between muscle strength and global health status (r=0.282, p=0.011), PF (r=0.373, p=0.001), RF (r=0.26, p=0.02) whilst no correlation with EF (r=-0.68, p=0.549), CF (r=0.038, p=0.738), and SF(r=0.214, p=0.056).

Conclusions

Muscle strength was correlated with quality of life, specifically in global health status, physical functioning, and role functioning in breast cancer patients. Overall, nearly all of the domains have good outcomes. Further assessment in patients’ nutritional status and physical activity were needed.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

23P - Oncotype DX RS correlation with clinicopathologic risk factors and chemotherapy: Follow up based on TAILORx study (ID 996)

Presentation Number
23P
Lecture Time
09:00 - 09:00
Speakers
  • Faroug S. Ali (Doha, Qatar)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Oncotype DX RS estimates the likelihood of recurrence and predicts the benefit from chemotherapy in early HR positive, node negative breast cancer. Patients are categorized into one of three tiers based on a calculated recurrence score (RS); low (<18), intermediate (18–30), and high (≥31–100). 2008 NCCN guidelines recommended adjuvant endocrine therapy for low RS, adjuvant chemoendocrine therapy for high RS. There was no clear chemotherapy recommendation for intermediate RS. In 2018 the TAILORx re-established RS categories; a score of less than 11 is low, 11-25 is intermediate and 26-100 is high, and provided evidence to treat patients with intermediate RS. We are Studying Oncotype Dx RS correlation with clinic-pathologic risk factors, and chemotherapy based on TAILORx tiers. We also looked the characteristics of patients with cancer recurrence.

Methods

Retrospective review of patients who had Oncotype DX test during 2012-2017 at National Cancer Center–Qatar.

Results

Of 54 patients studied 16(29.63%) had low RS, 32(59.26%) had intermediate RS, and 6(11.1%) had high RS. Univariate analysis showed that age (p<0.014), tumor grade (p<0.034), and Ki67% (cut-off 20%; p<0.013) were significantly different among Oncotype DX RS categories. There was no significant difference among Oncotype DX RS categories for tumor size (p<0.288) or PR status (cut-off 1%, p<0.3). Multivariate analysis showed that none of the clinical/pathological factors significantly predict the Oncotype DX RS. Chemotherapy was given to 1/16 (6.25%) patients with low, 7/32(21.9%) patients with intermediate, and 4/6 (66.7%) patients with high Oncotype DX RS (univariate analysis p<0.01). Tumor size was the only predictor of chemotherapy in multivariate analysis (OR 2.33 CI 0.33 - 3.86, p<0.020). 75% of patients who relapsed had RS 16-25, and were less than 50 years old in age.

Conclusions

Oncotype RS correlates significantly with individual clinical risk factors including age, tumor grade, Ki67%, chemotherapy treatment. Tumor size significantly predicts adjuvant chemotherapy. Breast cancer recurrence was noticed in younger patients with high intermediate RS (16-25), and adjuvant chemotherapy may be a reasonable option for these patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

24P - The Pink Vans: Bringing cancer screening closer to home (ID 193)

Presentation Number
24P
Lecture Time
09:00 - 09:00
Speakers
  • Frederic Ivan L. Ting (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

A global survey reported that among 15 Asian countries, the Philippines has the highest breast cancer mortality rate and the lowest mortality-to-incidence ratio. Studies have described socioeconomic factors as one of the major causes for the lack of access to early detection and treatment.

Methods

In response to this gap in the delivery of services to promote early cancer detection and in line with the Breast Health Global Initiative’s call for low and middle income countries to adopt breast cancer screening to the local context, the University of the Philippines – Philippine General Hospital Cancer Institute (UP-PGH CI) established the Mobile Breast Cancer Diagnostic Clinic Program, a first in the country -two pink vans that are fully equipped to reach far flung areas and provide breast cancer screening strategies are sent out to deliver services.

Results

In the first 6 months of the program’s existence, the pink vans were able to visit 3 strategically identified areas in the country. These three tours served a total of 189 women who all underwent mammography. Of these women, 18 had their suspicious lesions biopsied. Two-thirds of which were found to be malignant. These patients were then advised to follow-up at our institute for further work-up and management.

Conclusions

As the Philippine health department continues to emphasize clinical and self-breast exam as part of its breast cancer control program, efforts like the UP-PGH “Pink Vans” may eventually help supplement the gap in the country’s breast cancer screening endeavors.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

25P - Identification of gene mutations in patients with breast cancer in a region located in the southeast of the European part of Russia (ID 268)

Presentation Number
25P
Lecture Time
09:00 - 09:00
Speakers
  • Alexander Sultanbaev (Ufa, Russia, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

It is known that breast cancer is a complex heterogeneous disease due to the presence or absence of overexpression of receptors on the surface of tumor cells that correlate with the presence of penetrant mutations. Malignant neoplasms are considered as genetic diseases if they are characterized by multiple mutations in the genome, or epigenetic changes at the DNA level. Hereditary forms of malignant neoplasms occupy a special position due to their frequent development at a young age.

Methods

The study was carried out using next-generation sequencing-NGS. A genetic blood test was performed on 30 patients with breast cancer.

Results

As a result, highly penetrant mutations in the BRCA1, BRCA2, CHEK2, PALB2, RAD50 genes were revealed in 30 patients. Of the total share of probands in the BRCA1 gene mutations were detected with a mutation of 5382insC - 12 patients, c.3143delG- 3. In the BRCA2 gene of patients mutation c.6621_6622del- in 2 people and s. -39-1_-39delGA- in 1 patient. Using IHC a basal-like subtype breast cancer was established in all patients. The mutations were detected in the CHEK2 gene in 5 patients: c.470T> C- in 3 patients with a luminal B (HER2 positive) subtype; c.444 + 1G> A- in 2 patients with HER2 positive (non-luminal). In the PALB2 gene of cases: all 4 people with a basal-like subtype with the 1592delT mutation. The mutations c. 2157delA were detected in the RAD50 gene in 3 patients: of which 2 had luminal B (HER2 negative), 1 had luminal A subtype of breast cancer.

Conclusions

A next-generation sequencing method has significantly improved the efficiency of detecting mutations in the genes responsible for hereditary breast cancer. Pathogenic mutations in the BRCA1 / 2, CHEK2, PALB2, RAD50 genes were found of patients with a hereditary feature of the disease (proband has 1 to 3 blood relatives with malignant neoplasms). The identification of highly penetrant mutations in probands allowed us to determine their relatives, the expectable carriers of mutations, which were informed of the need genetic counseling.

Legal entity responsible for the study

Sultanbaev Alexander.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

26P - Body mass index and clinical outcomes in Egyptian women with breast cancer: A multi-institutional study (ID 376)

Presentation Number
26P
Lecture Time
09:00 - 09:00
Speakers
  • Amrou Mamdouh Abdeen Shaaban (Shuwaikh, Kuwait)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The aim of this work was to evaluate the association between body mass index (BMI) and clinical outcomes among Egyptian breast cancer patients.

Methods

We reviewed the file registry of 629 patients with operable breast cancer regarding age, sex, height, weight, family history of breast cancer, menopausal status, tumor characteristics, TNM classification, and treatment during the period from January 2006 to December 2012. In our analyses, obesity was defined as a BMI of ≥30 kg/m2. The primary objective was to estimate the effect of obesity on the clinical outcomes of breast cancer patients including DFS and OAS.

Results

A total of 629 patients with a mean age of 51.1 years. Stage III and Stage II presented 52% and 46.6% respectively. Overweight and obese patients represent 60.5% of all patient population. there was no association between tumor stage, grade or menopausal status and BMI. Patients with normal BMI showed a median survival of 95.3 months [ CI: 54.6,136.06]. This was significantly higher than overweight and obese patients (p = 0.001). Nearly one-third of patients (29.1%) with normal BMI experienced disease relapse compared to 32.8% for overweight and obese patients, however, this was statistically not significant (0.097).

Conclusions

According to the results of this retrospective study, Obesity is an independent prognostic factor for OS in patients with operable breast cancer.

Legal entity responsible for the study

Minia University Hospital and Mansura University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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27P - Breast cancer primary site and laterality as predictive factors of prognosis: SEER based analysis for survival (ID 425)

Presentation Number
27P
Lecture Time
09:00 - 09:00
Speakers
  • Eman I. Zin Eldin (Menoufia, Egypt)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer prognostic factors vary from pathological grades, hormonal sensitivity, stage and LN metastasis. Results from recent studies discuss primary location as survival indicator but its significance still unclear. With SEER database registry in place, a rich source for data collection with differentiating breast cancer sites and primary location. With analysis of these data, the effect of cancer's primary origin on breast cancer survivorship would be more comprehensive.

Methods

Using SEER*stat 8.3.6 program, Based on Incidence - SEER Research Data, 9 Registries, Nov 2019 Sub (1975-2017), patients diagnosed with breast cancer (site recode ICD-O-3) between 1975-2017 are selected. Case listing session was done with extraction patients year of diagnosis, survival time in months, laterality, and primary site. Cox regression was done using IBM SPSS statistics 25. p-value <0.001 is considered significant.

Results

720272 patients were involved in analysis (50.9% left:49.1% right origin of primary). Median survival time for the cohort was 185 months(95% CI:184.4:185.5). Left side malignancy showed a significantly less positive effect on survival than right originated ones (HR, 0.988; 95% CI, 0.982–0.995). The upper and lower inner quadrants show a significantly higher effect on survival (HR, 1.877; 95% CI, 1.797–1.960) and 1.761(1.685). (HR, 1.761; 95% CI, 1.685–:1.842) respectively P-value <0.001.

P-value HR 95.0% CI for HR
Lower Upper
Nipple Reference
Central portion of breast <0.001 1.454 1.391 1.521
Upper-inner quadrant of breast <0.001 1.877 1.797 1.960
Lower-inner quadrant of breast <0.001 1.761 1.685 1.842
Upper-outer quadrant of breast <0.001 1.567 1.501 1.635
Lower-outer quadrant of breast <0.001 1.711 1.637 1.788
Axillary tail of breast <0.001 1.142 1.078 1.211
Overlapping lesion of breast <0.001 1.680 1.610 1.754
Breast, NOS <0.001 1.350 1.293 1.410

Hazard ratios for primary site of breast cancer: Cox regression analysis Optimal cut-offs were determined with a maximal chi-square method.HR: hazard ratio; CI: confidence interval; NOS: not otherwise specified

Conclusions

Upper and lower inner quadrants show the best survival for patients diagnosed with breast cancer. The primary site of malignancy in breast cancer appears to be a good predictive value of survival and can be used as a rough method to predict patients` prognosis. More Data extraction, analysis, and interpretation of overall and cause-specific survival are recommended for more knowledge about the primary site in depth.

Legal entity responsible for the study

Mohamed Alaa Gouda.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

28P - Breast cancer care services at Nilai Medical Centre: A Malaysian experience (ID 496)

Presentation Number
28P
Lecture Time
09:00 - 09:00
Speakers
  • Ratnavelu Kananathan (Nilai, Negeri Sembilan, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Introduction and Rationale. Nilai Medical Centre was established on 1999 in Nilai Negeri Sembilan. In a partnership with Malaysian Health Travel Council data was collected prospectively using the HPMRS platform. HPMRS is a locally developed data base system to measure health care performance and reporting. For the purpose of measuring breast cancer performances, we mostly adopted the performances measures developed and used by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comphressive Cancer Network and National Accreditation Program for Breast Cancer.

Methods

Data Data was reported to HPMRS by year of reporting according to the centre participating in MHTC’s PHTE program. A total of 226patients were reported from 2010 till 2014. 76 patients were ineligible for inclusion while 53 patients had incomplete data for analysis and were excluded from analysis.

Results

The Aged ranged from 33 to 79 with a mean of 51years, 43% were aged <50years. 41% Chinese, 38% Malays and 20% Indians. 41% Early Breast Cancer, 35% Locally Advanced Cancer and 16% metastatic Breast Cancer. Receptor states were 55% positive for ER,43% PR and 31% for HER2. 19% had Triple negative breast cancer. Breast Cancer Care Performances The overall Breast Cancer care results was 98%. A 98% composite score means that the centre provided an evidence based Breast Cancer Treatment 98 times for ever 100 opportunities. Performances varied from as low as 50%(Trastuzumab treatment ) to a perfect score of 100% (Pathology report confirming malignancy, surgical treatment and radiotherapy) Survival Data The 5 years overall survival 99% Stage I, 83% Stage II,36% Stage III and 28% Stage IV. The relative survival at 5years was 99% Stage I and 97% Stage II indicating these patients were practically cured of their disease. This was far better then the results reported in Malaysian Study on Cancer survival of 87% in Stage I and 80% in Stage II. In the other stages NMC survival was 81.9% in Stage III and 50.4% in stage IV compared with 59% in Stage III and 23.3% in Stage IV in the Malaysia Study. NMC results were comparable with the SEER results( 2008 till 2014) as Early stage 99%,Localized Stage 85% and Distant stage 27%.

Conclusions

The results will set as a base line for future measurements.

Legal entity responsible for the study

Kananathan R.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

29P - Factors affecting breast self-examination (BSE) behaviour among female high school students in Denpasar City, Bali (ID 592)

Presentation Number
29P
Lecture Time
09:00 - 09:00
Speakers
  • Cindy G. Trisina (Denpasar, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is the most common type of cancer for women worldwide and in Indonesia. Breast cancer patients in Bali, especially in Denpasar, are mostly diagnosed during advanced stage. Among those late stage diagnosis, 40-50 years old being the most prevalent with young women (<40 years old) being above average in prevalence. Early detection such as Breast Self Examination (BSE) is very crucial to prevent late stage detection. Therefore, we aimed to evaluate factors affecting BSE behavior among female high school students in Denpasar City, Bali Province, Indonesia.

Methods

A pre-experimental cross-sectional study-based community was conduct on 11 January 2020 in Denpasar, Bali. The data is collected using a validated questionnaires to evaluate knowledge, attitude, behavior, information exposure, parent support, and peer support as factors affecting BSE behavior among female high school students. Data is analyzed using chi-square with p-value ≤0.05 is categorized as significant.

Results

82 respondents were involved in this study with a mean age of 15.93 ± 0,798 years. Mostly the students have high knowledge (63.4%), good attitude towards BSE (51.2%), BSE information exposed (58.5%), low parent support towards BSE (57.3%), and low peer support towards BSE (74.4%). The highest significant factor is knowledge (p= 0.001, OR=6.500), followed by BSE information exposed (p=0.003, OR=4.667), and peer support (p=0.023, OR=3.185).

Conclusions

We conclude that factors affecting BSE behavior among female high school students in Denpasar, Bali are knowledge, BSE information exposed, and peer support. We suggest greater attention in improving students’ knowledge, expose more information about BSE, and educate peer support towards BSE among female high school students in Denpasar, Bali.

Legal entity responsible for the study

Badan Semi Otonom Komunitas Mahasiswa Peduli Kanker Fakultas Kedokteran Universitas Udayana.

Funding

Badan Semi Otonom Komunitas Mahasiswa Peduli Kanker Fakultas Kedokteran Universitas Udayana.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

30P - Male breast cancer: A rural based peripheral cancer center experience (ID 759)

Presentation Number
30P
Lecture Time
09:00 - 09:00
Speakers
  • SACHIN KHANDELWAL (SANGRUR, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Male breast cancer (MBC) is an uncommon malignancy with an estimated incidence of less than 1 % of all breast cancer cases. It is a disease of elderly arising in 6th to 7th decade. Patients usually present at an advanced stage with early skin and nodal involvement. Age, testicular disorders, liver cirrhosis, exogenous estrogens, BRCA -2 mutations are proposed etiological factors. There are four Population based cancer registries (PBCR) in Punjab, India. Amongst them two are predominantly urban (Chandigarh and SAS Nagar) and two are predominantly rural (Sangrur and Mansa). Sangrur PBCR is based at Homi Bhabha Cancer Hospital (under aegis of Tata Memorial Center, Mumbai). The aim of this study is to look into the incidence and clinico-pathological characteristics of M.B.C at our institute, mainly catering to a rural population.

Methods

A total of 1735 breast cancer cases registered over a period of 4 ½ years from January 2015 to July 2019 were screened. Online records were accessed.

Results

A total of 34 M.B.C cases were identified amounting for 1.9% of all breast cancer cases. All patients were from Punjab except one. 44.1% were from district Sangrur. If we look at district wise ratio of MBC to total breast cancer cases then Barnala (2.3) is followed by Mansa (2.1) followed by Sangrur (2.09). Mean Age was 62.5 years. Mean BMI (N=20) was 23.9. Family history was not significant in any case. Tumor was localized to right in 64.7 % cases. Most of the tumors were central in location (70.6%). Main complaint was lump in 58.8%. 16 patients were metastatic,10 were LABC, 8 were early stage. All were infiltrating ductal carcinoma. 27 were ER +ve, 25 were PR +ve, 1 was her2neu positive, 1 was Triple negative. 7 patients were Luminal A, 8 were Luminal B, 1 was Basal, 6 were unknown due to missing information,12 were Luminal A/B. 13 patients were treated radically, 9 were palliative & 12 patients defaulted. 4 patients with oligo-metastatis treated radically were alive at last presentation. 2 patients underwent palliative mastectomy.

Conclusions

Our ratio of M.B.C to breast cancer cases is 1.9 % which is higher than average of 1%. Study period in our series is only 4 1/2 years unlike others, usually more than a decade, with equivalent number of cases. Unlike other studies our burden of metastatic disease was more.

Legal entity responsible for the study

Sachin Khandelwal.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

31P - The prognostic value of pre-treatment peripheral neutrophil-lymphocyte-ratio (NLR) and its correlation with mutant p53 expression in Indonesian triple negative breast cancer patients (ID 800)

Presentation Number
31P
Lecture Time
09:00 - 09:00
Speakers
  • Rosita Y. Purwanto (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Triple-Negative Breast Cancer (TNBC) represents an aggressive phenotype among other breast cancer subtypes with worst prognosis due to abundant inflammatory process. Recent pre-clinical study suggested a correlation between p53 inactivation and systemic inflammation response in driving breast cancer progression. In this study, we evaluated the prognostic value of pre-treatment NLR and its association with mutant p53 expression.

Methods

TNBC patients treated in of Dr. Sardjito General Hospital during 2014-2017 were retrospectively analyzed. Receiver Operating Curve (ROC) was utilized to determine the NLR cut off value and Kaplan Meier survival analysis was used to evaluate the 3-years overall survival (OS). To examine the correlation of NLR and p53, chi-square and independent t-test analysis were applied. Multivariate analysis was done using Cox Proportional Hazard Regression Model with adjustment for age, BMI, clinical staging, histological grading, subtypes, and therapy.

Results

A total of 53 TNBC patients were included in this study. The cut off value used to classify NLR into high and low NLR was 1.67 (AUC: 0.720, 95%CI: 0.581-0.859, p: 0.007, sensitivity: 87.1%, specificity: 50.0%). Mutant p53 expression was associated with high NLR (p= 0.013) with significant difference (Mean difference: 0.611, 95%CI: 0.425-1.179, student’s t-test p: 0.036). Patients with high NLR showed worse 3-years OS than patients with low NLR (Median OS±SE (months): 21.205±2.356, 95%CI: 16.588-25.823 vs unreached, p: 0.006). NLR was an independent prognostic factor of TNBC based on multivariate analysis (HR: 3.705, 95%CI: 1.176-11.666, p: 0.025).

Conclusions

Mutant p53 expression was associated with high NLR and, furthermore, NLR was an independent prognostic marker for TNBC. Therefore, this combination has the potential to stratify TNBC patients’ risk and further study is needed to formulate the stratification system.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

33P - FDG-PET predictivity of pathological axillary nodal status in carcinoma breast-upfront and post-neoadjuvant chemotherapy (NACT) setting (ID 161)

Presentation Number
33P
Lecture Time
09:00 - 09:00
Speakers
  • Krithikaa Sekar (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

FDG PET is used in staging, early prediction of treatment response, monitoring metastatic tumours and in disease status assessment post completion of treatment. In patients undergoing upfront surgery, a significant standardized uptake value (SUV) is associated with pathological node positivity. In patients receiving anterior chemotherapy, studies have shown that a reduction in size and SUV of primary tumour or involved node predicts response to therapy. However based on our observation, the predictive value of PETCT appeared to differ between the upfront setting and post-neoadjuvant chemotherapy (NACT) setting. Our study compares the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG-PET in predicting pathological axillary nodal involvement in 50 upfront surgery and 50 post-NACT patients.

Methods

This study was conducted between the years 2015 to 2016. Clinical, histopathological and radiological details were obtained from patient records. 50 upfront surgery and 50 post-NACT patient details were reviewed for PETCT nodal status and histopathological nodal status and the following parameters analysed. 1)Sensitivity; 2)Specificity; 3)Positive Predictive Value; 4)Negative Predictive Value

Results

In upfront surgery cases the total number of TP was 21, FP was 2, FN was 12 and TN was 15. In post NACT setting, it was 5, 1, 10 & 34 respectively.

Upfront PETCT Post NACT PETCT
Sensitivity 63.6% 33.3%
Specificity 88.2% 97.1%
Positive Predictive Value 91.3% 88.3%
Negative Predictive Value 55.3% 77.2%

Conclusions

Although metabolic response monitoring post chemotherapy is a useful tool,the sensitivity appears to be lower in predicting pathological node positivity. That is, the proportion of patients with positive pathological node having PET positivity appears to be lower. A practical application of the same would be, to complete all cycles of chemotherapy prior to surgery, irrespective of an interim PETCT complete nodal response, to attain maximal Pathological Complete Response rates.To conclude, the rate of PETCT predictivity of pathological axillary nodal positivity appears to differ between upfront surgery and post-NACT setting.

Legal entity responsible for the study

Krithikaa Sekar.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

34P - Clinical significance of neoadjuvant dose-dense chemotherapy for II and III stage breast cancer: A meta-analysis of published studies (ID 626)

Presentation Number
34P
Lecture Time
09:00 - 09:00
Speakers
  • Meng chen Liu (Shijiazhuang, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For Ⅱ and Ⅲ stage breast cancers (BCs),neoadjuvant chemotherapy (NCT) is typically the initial treatment.However, there is no evidence to support an improvement in efficacy with dose-dense (DD) chemotherapy (CT) in this setting. Results from clinical trials of neoadjuvant DD-CT in patients with breast cancer are inconsistent.This systematic review evaluates whether DD-CT was more effective than the standard-schedule CT.

Methods

This meta analysis included all comparative prospective and retrospective studies published in Pubmed, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science and the CNKI databases over the past 10 years.The studies that compared the DD-CT with a standard-schedule CT met our inclusion criteria.The primary outcomes were pathologic complete responses (ypT0N0M0: pCR). The secondary outcomes were disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) for pCR and Risk ratios (RRs) for DFS and OS were estimated and pooled.

Results

Eight studies involving 2477 patients were included in this meta-analysis. Of these, 1214 patients were treated with DD-CT and 1263 patients were treated with CT. The primary outcomes included 8 studies while the secondary outcomes included 7 studies. The pooled rates of the pCR were 19.4% and 11.9% in the experimental and control arms respectively. A significant increase in the pCR [OR= 1.74, 95% confidence interval (CI) 1.38–2.18, P < 0.00001] was noted with DD-CT. Dose-dense treatment also improved DFS[RR= 0.78, 95%CI 0.63–0.98, P = 0.03] and OS [RR= 0.81, 95%CI 0.68–0.96, P = 0.01]. However there was some heterogeneity.Similar results were observed in the further analysis, which was supported by our sensitivity analyses.

Conclusions

The meta-analysis demonstrated that DD-NCT significantly increased the pCR of Ⅱ and Ⅲ stage breast cancer compared with standard-schedule CT. Adjuvant dose-dense regimens can also improve DFS and OS.Taking into account the actual improvement in clinical efficacy,prognostic valueand the acceptable safety profile, DD-CT can be considered a standard approach for neoadjuvant therapy in Ⅱ and Ⅲ stage breast cancer.

Legal entity responsible for the study

The Fourth Hospital of Hebei Medical University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

35P - Pathological response to weekly nabpaclitaxel and carboplatin followed by anthracycline regimen in triple negative breast cancer (ID 959)

Presentation Number
35P
Lecture Time
09:00 - 09:00
Speakers
  • Goteti Sharat Chandra (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pathological complete response (pCR) is considered a potential surrogate marker for survival in triple negative breast cancer (TNBC), thus attracting strategies to achieve higher pCR. Addition of carboplatin to standard neoadjuvant chemotherapy regimen has been seen to increase pCR.

Methods

We aimed to evaluate efficacy of nab paclitaxel and carboplatin followed by dose dense anthracycline regimen by pCR in women with locally advanced tnbc. Patients with confirmed stage 2 or 3 were included. Hormone receptor and her 2 neu receptor status was confirmed by IHC and/or FISH. Patients received 12 weekly nab paclitaxel 125 mg/m2 plus carboplatin AUC 2 followed by dose dense doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 for 4 cycles and subsequent surgery. pCR was defined as absence of any disease in breast and axilla on surgical specimen. Secondary end points were breast conservation rates, progression free survival and toxicities.

Results

35 patients with confirmed stage 2 (20%) and stage 3 (80%) were treated between January 2017 and December 2020.The median age of patients was 48.7 years (26 – 71). pCR was achieved in 62.8 % (22) and remaining patients had partial response 34.2% (12). One patient showed stable disease on pathological specimen. Breast conservation surgery (BCS) was possible in 60 % (21). Of those who achieved pCR, 68 % (15) underwent BCS. Grade 3/4 toxicities were fatigue 2.8 % (1), thrombocytopenia 8.5 % (3), nausea/vomiting 2.8 % (1), peripheral neuropathy 2.8 %(1), febrile neutropenia 17 % (6) and anemia 14.2% (5). Hematological toxicity was tackled with reduction of carboplatin dose to AUC 1.5. Dose modifications were done in 63 % of patients. Anemia (74.2%), neutropenia (80%) and thrombocytopenia (71.4%) were most common all grade toxicities. After a median follow up of 25 months, median progression free survival was 68 % as per Kaplan-Meier analysis.

Conclusions

Nab paclitaxel and carboplatin followed by anthracycline regimen as neo adjuvant regimen led to impressive pCR rate of 62.8% in our study. Regimen was tolerated well with necessary dose adjustments showing good response rates with a trend towards increased progression free survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

36P - Survival in patients with contralateral breast cancer (ID 962)

Presentation Number
36P
Lecture Time
09:00 - 09:00
Speakers
  • Sergey Kamishov (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Survival in patients with contralateral breast cancer Kamishov S.V., Izrailbekova K.Sh. Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent. Survival data are not readily available in many developing countries due to inadequate information systems to collect reliable data on cancer mortality. Not all cancer patients die from cancer. Thus, cancer and other causes of death act independently or simultaneously. A cohort study was conducted to identify risk factors for contralateral breast cancer and to determine whether there was any significant difference in survival among patients with unilateral breast cancer (UBC) and patients with primary contralateral breast cancer (PCBC).

Methods

The study group consisted of patients with breast carcinoma as the first invasive primary cancer, diagnosed in 2012-2019 (n = 3492) at the Republican Special Medical Center for Medical and Rehabilitation of Uzbekistan, Tashkent). They were under surveillance until December 31, 2019. All patients undergoing treatment are monitored in accordance with the observation protocols of the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan In this study, the follow-up loss was 10% in UBC patients and 7.5% in PCBC patients.

Results

A total of 3492 cases of breast cancer were diagnosed at the RSPMCHR from 2012-2019. The analysis included all patients with UBC who did not develop a second cancer (n = 3163) and patients with PCBC who developed contralateral breast cancer (n = 67). The relative survival rates between younger, middle-aged, and older women with PCBC were significantly different from each other (p = 0.001). The differences in the relative survival rates of young, middle-aged and older women with UBC were not statistically significant (p = 0.4).

Conclusions

Despite the small sample size, the present study shows that early diagnosis has a survival advantage in breast cancer. In addition to organizing mammographic screening, in developing countries, educational programs are needed to raise awareness of cancer in order to detect breast cancer at an early stage and reduce mortality.

Legal entity responsible for the study

Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent.

Funding

Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

37P - Correlation between haematological toxicity with quality of life in breast cancer patients after first-cycle chemotherapy (ID 503)

Presentation Number
37P
Lecture Time
09:00 - 09:00
Speakers
  • Felix Wijovi (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy, as one of the main therapies to treat breast cancer, may result in undesirable side effects. It may disrupt the haematological system and cause disorders as a result of chemotoxicity. This condition may lead to a declining in Quality of Life (QoL) of the patients. There were limited data reported from Indonesia about the correlation between haematological chemotoxicity and QoL. Thus, the aim to find the association between them.

Methods

This was a cohort-prospective study which includes 50 breast cancer patients who undergone first-cycle of chemotherapy. Patients who had haematological abnormalities and poor quality of life before chemotherapy were excluded. Patient’s QoL was measured by QLQ-BR23 questionnaire which includes body image (BI); sexual functioning (SF); sexual enjoyment (SE); future perspective (FP); and functional total (FT). Haematological chemotherapy toxicity was determined by the number of haemoglobins, leukocytes count and platelet count. Chemotherapy toxicity is graded from 0 (no toxicity) to 5 (death) according to the National Common Institute Common Terminology Criteria for Adverse Events. Correlation is analysed with Pearson Correlation using SPSS version 25.0.

Results

65 patients were included in this study (mean age 46.98 ± 9.05). The correlation between haematological chemotoxicity and BI; SF; SE; FP; and FT were described as follow: Hb r = -0,3; -0.251; -0.498; -0.345; and -0.61 respectively, with p = 0.08; 0.044; 0.01; 0.283; and 0.02 respectively. Leukocyte r = -0.41; -0.121; -0.128; -0.7; -0.3 respectively, with p = 0.01; 0.3; 0.3; 0.02; 0.05 respectively. Platelet r = -0.123; -0.31; -0.7; -0.9; -0.042 respectively, with p = 0.3; 0.03; 0.04; 0.1; 0.05 respectively.

Conclusions

We found that Hb and platelet level is significantly correlated with sexual functioning, sexual enjoyment, and functional total. Meanwhile, the leukocyte level is significantly correlated with body image, future perspective, and functional total.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Breast cancer, locally advanced (ID 1142)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

38P - Evaluation of the prognostic value of innate immunity-related biomarkers in early breast cancer (BC) (ID 872)

Presentation Number
38P
Lecture Time
09:00 - 09:00
Speakers
  • Veronica Martini (Novara, Italy)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

CD47 and SIRPα (signal-regulatory protein) are tumor biomarkers of innate immunity, expressed on cancer cells and tumor associated macrophages (TAMs); their interaction provides a “don’t eat me” signal that impairs phagocytosis. The relationship between CD47/SIRPα expression and BC aggressiveness has been investigated, however, its prognostic role is not clarified. With these premises, we have assessed the distribution and the possible prognostic value of CD47/SIRPα expression in early BC.

Methods

To verify our hypothesis, we first used in silico data from GOBO and GEPIA, two publicly available datasets: GOBO is a public repository containing microarray data (Affymetrix U133A) from 1881 early BC patients, with a median follow up of 120 months. GEPIA is a web server for analysing RNA expression data of tumours and normal samples from the TCGA and the GTEx projects, by a standard processing pipeline. Immunohistochemical (IHC) analyses were retrospectively performed on formalin-fixed paraffin embedded tissue (FFPE) samples in a cohort of 105 BC patients referred to our institution. The association between CD47 and SIRPα expression levels and outcome was evaluated using the χ2 test. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier life table method.

Results

In silico data showed that CD47 and SIRPα are preferentially expressed in triple negative (TN) BC, as compared to other BC subtypes (p< 0.0001). CD47 upregulation is associated to a worse OS only in Luminal A BC (GOBO p<0.001, n= 189 patients). By IHC analysis in our retrospective series, CD47 was overexpressed in 80% of TNBC and in 56% of Luminal BC samples. Of note, SIRPα was expressed in 20% of TAMs and in 50% of TN BC samples.

Conclusions

Biomarkers of innate immunity are represented but differently expressed in the different BC subtypes; IHC analyses are ongoing to consolidate this result and to assess their prognostic role in our patient cohort. Final analyses will be presented.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

39P - CSF-1R inhibitor (C019199) enhances antitumor effect in combination with anti-PD-1 therapy on murine breast cancer models (ID 822)

Presentation Number
39P
Lecture Time
09:00 - 09:00
Speakers
  • Jiani Zheng (Xiamen, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Colony-stimulating factor-1 (CSF-1) is the primary regulator of mononuclear phagocytic cells. CSF-1 plays an important role in recruiting macrophages to tumor environment. Overexpression of CSF-1 and its ligand, colony-stimulating factor-1 receptor (CSF-1R), have been reported to be associated with the development of various types of cancers, such as breast, ovarian, and colorectal cancer. This study aims to investigate the treatment effects of a new CSF-1R inhibitor named C019199 in murine breast cancer (BC) models when administered alone or in combination with anti-PD-1 antibody.

Methods

Inhibition of CSF-1R was investigated in the murine bone marrow derived macrophages (BMDMs) for cell-based assay. Furthermore, the immunocompetent Balb/c mice were subcutaneously implanted 4T1 breast cancer cells in the right flank. Mice were randomized into groups of 9 and treated with C019199 (orally, 30 mg, 60mg or 120 mg/kg/d), either alone or in combination with anti-mouse PD-1 antibody (intraperitoneally, 10 mg/kg). 1 of 9 groups was treated with single-agent Docetaxel (intraperitoneally, 10 mg/kg). The animal body weight and tumor growth were monitored twice a week. Results were analyzed by 2-way ANOVA with Bonferroni's test.

Results

1. C019199 inhibited the murine colony-stimulating factor-1 receptor (CSF-1R) with an IC50 of about 8.0nM in cell-based assay. 2. C019199 inhibited tumor growth in murine BC models. The combination of C019199 and anti-PD-1 had better synergistic antitumor efficacy than single-agent. Balb/c mice implanted 4T1 cells were treated with C019199 alone or combined with anti-PD1 for 14 days. The antitumor efficacy and treatment detail (Table) were detected.

Effect of C019199 on body weight and tumor size in murine 4T1 breast cancer models

Group Administration regimen Tumor size (mm3,Mean±SEM) Rate% of average body weight change
Day 0 Day 14
Vehicle QD x 14 67.11 ± 3.01 1705.69 ± 130.96 13.76%
Anti-mPD-1 Day 0, 3, 7, 10 66.82 ± 3.05 1343.55 ± 118.65 16.43%
Docetaxel Day 0, 7 66.88 ± 3.11 1023.00 ± 68.19**** 4.21%
C019199 QD x 14 67.07 ± 3.17 1074.32 ± 59.31**** 11.01%
C019199 QD x 14 66.76 ± 3.05 927.24 ± 65.68**** 7.97%
C019199 QD x 14 66.69 ± 2.99 671.71 ± 62.56**** 2.18%
Anti-mPD-1 Day 0, 3, 7, 10 66.62 ± 2.94 1079.65 ± 64.05**** 13.25%
C019199 QD x 14
Anti-mPD-1 Day 0, 3, 7, 10 66.53 ± 2.86 794.21 ± 105.82**** 10.50%
C019199 QD x 14
Anti-mPD-1 Day 0, 3, 7, 10 66.41 ± 2.72 619.62 ± 25.10**** 4.85%
C019199 QD x 14

*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 compared with vehicle group. SEM, standard error of mean.

Conclusions

C019199 is a new tyrosine kinase inhibitor of CSF-1R. Single-agent C019199 showed dose-dependently inhibition in murine 4T1 BC tumors. C019199 combined with anti-PD-1 had better antitumor efficacy than C019199 alone. Assessed by animal body weight, such combination therapy was well tolerated. The mechanisms of C019199-mediated immunomodulatory effects in combination with anti-PD-1 need further exploration.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

40P - Molecular subtypes and imaging phenotypes of breast cancer: MRI (ID 904)

Presentation Number
40P
Lecture Time
09:00 - 09:00
Speakers
  • Yulduz N. Khatamovna (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study aimed to examine MRI dynamic contrast-enhanced (DCE) imaging in various histological and molecular biological types of breast cancer.

Methods

To solve the set tasks, a clinical and instrumental examination was carried out of 70 women with a verified diagnosis of breast cancer who were examined and treated at the RSSPMCO&R in 2017–2019. The age of the patients was 26–75 years (mean age - 49.0 ± 2 years).

Results

For luminal A cancer (22 of 70 cases), the following MR signs were revealed: nodular formations more often had an irregular shape - 21 (95.5%), irregular (59.1%), less often spicular contours (27.3%). In 16 of 22 cases, a ring-shaped contrasting pattern was noted. Type III intensity-time curve at MRI with DCE was found in all 22 patients with luminal A subtype of breast cancer. It should be noted that all additional MR signs (retraction of the nipple, thickening and deformation of the skin over the formation) were found in luminal subtype A. The luminal B-subtype was detected in 20 patients (28.6%), with Her2/neu-positive luminal B-subtype noted in 12 patients, and Her2/neu-negative subtype in 8 cases. For these two subtypes of the masses visualized on MRI images were the same (irregular shape with indistinct contours, annular contrasting), but 4 of 12 patients with luminal Her2/neu-positive subtype had type II on MRI with DCE. The same type of curve was observed in 5 out of 11 patients (45.5%) with Her2/neu-positive breast cancer. At the same time, with luminal, subtype, luminal, Her2/neu-negative subtype, and three cases of negative breast cancer, type III of the dynamic contrast curve was always observed. Consequently, type II of the curve was observed only with negative Her2/neu types. In our studies, in 53% of triple-negative subtypes breast cancer was displayed on MR images with a rounded-oval or lobular shape, and in 17.6% with clear smooth (smooth) contours. But type III “intensity - time” curve, noted according to MRI data with DCE, testified to the malignant process in all 17 patients with triple-negative breast cancer.

Conclusions

Our studies have shown that the pathologically determined degree of differentiation of breast cancer and immunohistochemical types and subtypes affect the visualized morphological characteristics and its functional features, assessed by MRI with DCE.

Legal entity responsible for the study

Nishanova Yulduz.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

42P - Impact of germline mutations on breast cancer prognosis in Kazakh population (ID 1029)

Presentation Number
42P
Lecture Time
09:00 - 09:00
Speakers
  • Dilyara Kaidarova (Almaty, Kazakhstan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer (BC) shows a high incidence both in Kazakhstan and worldwide. Presence of BRCA1 and BRCA2 genes defects, as well as non-BRCA genes can increase the risk of BC and they are still under study. There is evidence of the effect of germline mutations on the survival outcomes of breast cancer patients, according to the molecular characteristics of the tumor in different subgroups.

Methods

The study enrolled 235 unrelated patients from the Kazakh population (the average age 34.25 ± 4.56) with BC. Genomic DNA was obtained from peripheral blood and sequencing was performed using TruSight Cancer Kit on the MiSeq platform.

Results

Bioinformatics analysis of NGS data identified 64 pathogenic variants, the heterozygous state were found in 62 (26.4%) patients, 8 (12.5%) variants were not previously described in databases.The most frequent pathogenic mutations were in the genes BRCA1 (24 variants (37.5%) and BRCA2 (18 (28.1%)). Additional pathogenic variants were identified in the non-BRCA genes (APC, ATM, BLM, CHEK2, PALB2, TP53, ERCC2, FANCA, FANCM, NBN, PMS1, PMS2, SDHB and XPA). 84 of the patients (43.3%) had early stage BC, 101 (52.0%) locally advanced, 9 (4,6%) with advanced forms of BC. 45 (23.2%) had disease progression after complex treatment: bone mets in 10 cases, 6 patients had liver mets, 11 lung and 6 patients had brain mets, 12 had combination of different metastases- visceral crisis. 6 cases showed cancer-related death, 5 of them had metastasis in CNS. Luminal A and B was in 27 (13.9%) and 81 (41.7%) cases, 20 (10.3%) patients had Her2-enriched, and 64 (32.9%) had triple-negative subtype of tumor according IHC. The triple-negative molecular subtype of the tumor was found most in the BRCA1-associated group, almost two times higher than in the group of patients without pathogenic mutations (58.3% versus 29.5%, χ2 = 9.45, p = 0.002), the difference is statistically significant. Her2-enriched and triple-negative subgroups had worse OS than Luminal subtypes (hazard ratio, HR 1.20 95% CI: 1.12-1.51) and worse OS, showing 3 patients with a combination of pathogenic BRCA1/2, CHEK2, PALB2, TP53 mutations.

Conclusions

The presence of germline mutations in combination with aggressive subtypes significantly decreases overall survival in young women with breast cancer in the Kazakh population.

Legal entity responsible for the study

Kazakh Institute of Oncology and Radiology.

Funding

Ministry of Healthcare of Kazakhstan.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO2 - Trastuzumab associated cardiotoxicity presenting with features of Left anterior descending occlusion on Echocardiography - a Young oncologist case report. (ID 214)

Presentation Number
YO2
Lecture Time
09:00 - 09:00
Speakers
  • Rahul D. Arora (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

Background

Alterations in cardiac energy metabolism pathways have been postulated as the underlying cause of trastuzumab induced toxicity in cardiomyocytes.

Case details

49 year old female, a case of ER positive, PR positive, HER - 2 /neu positive, infiltrating ductal carcinoma of Right breast with history of undergoing mastectomy with sentinel lymph node dissection (pT3N0) and having recieved four cycles of adriamycin plus cyclophosphamide in the adjuvant setting, followed by seven cycles of weekly paclitaxel, and five cycles of trastuzumab ( at three weekly intervals). She was planned for trastuzumab with hormonal therapy and radiotherapy. She presented with complaints of chest tightness, with history of radiation to both shoulders since the past one week. The pain improved upon rest and was not associated with breathlessness, swelling of the legs, fever or cough. She had undergone an echocardiogram prior to the initiation of her chemotherapy which showed an ejection fraction of 55 percent along with normal left ventricular systolic function and grade I LV diastolic dysfunction. ECG done at that time was normal. Her recent ECHO showed an ejection fraction of 45 percent along with grade I diastolic dysfunction. Hypokinesia was noted in the apical and lateral region in the territory of the left anterior descending artery with left ventricular systolic dysfunction. While, the reduction in the ejection fraction was along expected lines, the occurrence of hypokinesia in the absence of a past medical history of hypertension and diabetes mellitus was an unexpected finding. Upon, further evaluation, the fourth and fifth dose of her targeted therapy had been delayed due to the ongoing SARS Cov – 2 pandemic. She had received a higher than usual dose of trastuzumab (8 mg from 6 mg previously) in the last setting. She was advised to review with medical oncology and counselled about the possibility of ischemic cardiac disease due to HER 2 targeted therapy.

Conclusion

A “probable” rating on the Naranjo algorithm for assessing adverse events and “possible” causality on the WHO Uppsala monitoring centre causality assessment monitoring scale was obtained.

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e-Poster Display Session (ID 87) Poster Display

Breast cancer, metastatic (ID 1143)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

50P - Efficacy and safety analysis of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer: A retrospective study (ID 867)

Presentation Number
50P
Lecture Time
09:00 - 09:00
Speakers
  • Yijia Hua (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lapatinib has shown effectiveness in treating HER2-positive metastatic breast cancer, but therapies after lapatinib resistance are still controversial. In this retrospective study, we assessed the efficacy and safety of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer.

Methods

From August 2018 to March 2020, 76 HER2-positive metastatic breast cancer patients who previously failed by lapatinib received pyrotinib in four hospitals. The primary endpoint was investigator-assessed progression-free survival (PFS) per Respond Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoint was the overall survival (OS) and safety of pyrotinib.

Results

66 (86.8%) patients received pyrotinib immediately after lapatinib and 10 (13.2%) received pyrotinib following one or more other therapies. The median PFS of pyrotinib was 8.0 months (95%CI 5.1-10.9) and OS has not reached. Objective response rate (ORR) was 17.1%, and clinical benefit rate (CBR) was 60.5%. Patients who benefited from lapatinib ≥6.0 months were found to have a longer PFS (P=0.034; stratified hazard ratio [HR] 0.534, 95%CI 0.293-0.975). In patients who had received lapatinib in 3 or later line therapy (35, 46.1%), the median PFS of pyrotinib was 9.9 months (95%CI 6.97-12.83) and was relevant to whether lapatinib PFS had reached 6.0 months (P=0.044; HR 0.412, 95%CI 0.167-1.013). No relations were detected between pyrotinib PFS and estrogen receptor (ER) status, trastuzumab resistance, brain metastasis or the sequential use of pyrotinib. In patients who had received lapatinib earlier (41,53.9%), the median PFS of pyrotinib was 6.4 months (95%CI 3.57-9.23). No relevant factors were observed. There was no difference in PFS between these two groups with different lapatinib lines. Toxicity profiles were similar in both groups. The most common adverse effects were diarrhea (34, 44.7%) and hand-foot syndrome (10, 13.2%).

Conclusions

Pyrotinib could improve the survival of HER2-positive metastatic breast cancer patients after the failure of lapatinib. For patients who benefited from lapatinib ≥ 6.0 months in 3 or later line therapy, pyrotinib could provide a clinically meaningful longer PFS.

Legal entity responsible for the study

The authors.

Funding

National Key Research and Development Program of China (ZDZX2017ZL-01), High-level Innovation Team of Nanjing Medical University (JX102GSP201727), Wu Jieping Foundation (320.6750.17006), Key Medical Talents (ZDRCA2016023), 333 Project of Jiangsu Province (BRA2017534 and BRA2015470), The collaborative innovation center for tumor individualization focuses on open topics (JX21817902/008) and Project of China key research and development program precision medicine research (2016YFC0905901).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

51P - Real world outcomes in elderly women with HER2-positive advanced breast cancer (ID 547)

Presentation Number
51P
Lecture Time
09:00 - 09:00
Speakers
  • Nicole Evans (Box Hill, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The development of anti-human epidermal growth factor receptor 2 (HER2) therapies has significantly improved disease outcomes in patients with HER2-positive advanced breast cancer (ABC). However, elderly patients are largely under-represented in clinical trials. We examined treatment patterns and outcomes in an elderly (defined as ≥70) ‘real world’ Australian population.

Methods

Data was extracted from the Treatment of Advanced Breast Cancer in the HER2-positive Australian Patient (TABITHA) multi-site clinical registry, and patients stratified according to age (<70 and ≥70 years). Descriptive statistics were used to report baseline characteristics and compared using T-tests and Chi square analyses. Treatment duration and overall survival were calculated via the Kaplan-Meier method.

Results

We identified 319 patients, including 67 patients (21%) aged ≥70 years. Older patients were more likely to have an Eastern Cooperative Oncology Group performance status of ≥2 (16% vs 3%; p<0.001) and a Charlson Comorbidity Index of ≥2 (13% vs 7%; p<0.001). There were no significant differences in hormone receptor status, de novo metastatic presentation, or presence of visceral disease. A similar proportion of patients in each group received first line HER2-directed therapy, and the duration of therapy was not significantly different. Despite no difference in the proportion of patients who received first-line chemotherapy, older patients demonstrated shorter chemotherapy durations (2.7 months vs 3.5 months; p<0.02). Median overall survival was significantly longer in younger patients (82.4 months vs 42.3 months; hazard ratio, 0.50; 95%CI, 0.29-0.87; p<0.001). In the first-line setting, adverse events rates were higher in the older group (34% vs 20%; p=0.04), including cardiotoxicity (7% vs 0.9%; p=0.02), and on-treatment deaths (5% vs 0%; p=0.01).

Conclusions

Elderly patients with HER2-positive ABC demonstrated shorter chemotherapy durations, poorer overall survival, and increased rates of adverse events despite having similar disease characteristics and treatment patterns. Prospective studies are required to improve outcomes in the elderly population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

52P - Chemotherapy selection in routine clinical practice in Japan for HER2-negative advanced or metastatic breast cancer (KBCRN A001: E-SPEC Study) (ID 534)

Presentation Number
52P
Lecture Time
09:00 - 09:00
Speakers
  • Yookija Kang (Osaka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Anthracycline-based (A) and taxane-based (T) chemotherapy (ChT) are standards of care for triple-negative (TN) or hormone-resistant advanced/metastatic breast cancer (AMBC) in 1st- or 2nd-line ChT. However, the choice of regimen for oncologists and patients is diverse, requiring consideration of not only survival benefit but also quality of life issues. We reported that most patients received eribulin (E) in 1st- or 2nd- line therapy in the Japanese real-world setting at the ESMO 2018 congress. Here, we report updated data regarding ChT sequences and treatment discontinuation.

Methods

We prospectively registered TN AMBC patients and estrogen receptor-positive and HER2-negative AMBC patients who relapsed during or within 6 months after the end of adjuvant endocrine therapy (ET) and were refractory to at least one previous ET. Patterns of ChT and their feasibility were evaluated (ClinicalTrials.gov No. NCT02551263).

Results

Between June 2015 and July 2017, a total of 201 patients were enrolled, 180 of whom were analyzed. The frequent 1st- and 2nd-line ChT sequences were as follows: T followed by E (n=33), oral FU-based therapy (FU) followed by E (n=26), E followed by T (n=21), T followed by FU (n=11), and E followed by FU (n=10). E was administered in 1st- or 2nd-line therapy for 60 patients who did not receive A, and for 35 patients who did not receive T. The main reason the attending physician chose E for patients who did not receive A was “reducing toxicity” in 38.3%, “non-life threatening” in 30.0%, and “patient preference” in 18.3%. Respective ratios in patients who did not receive T were 34.3%, 34.3%, and 20.0%. Patients treated with E or FU in 1st- and 2nd-line ChT had significantly less discontinuation due to adverse events than those with A/T (1st line: p=0.011, 2nd-line: p=0.036). In contrast, there was no statistical difference between E/FU and A/T in 3rd-line ChT (p=1.000).

Conclusions

This study showed that various 1st- and 2nd-sequence treatments including E were chosen in a real-world setting. The lower proportion of adverse events and lower discontinuation rate of E/FU in 1st- and 2nd-line therapy may be due to the better feasibility of these treatments.

Clinical trial identification

NCT02551263.

Legal entity responsible for the study

Kyoto Breast Cancer Research Network.

Funding

Eisai Co., Ltd.

Disclosure

T. Kagimura: Research grant/Funding (self): Eisai. T. Taguchi: Honoraria (self), Donation: Eisai. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

53P - Aromatase inhibitor and cyclin-dependent kinase 4/6 inhibitor treated HR+/HER2- metastatic breast cancer differ to those treated with Aromatase inhibitors alone on progression (ID 870)

Presentation Number
53P
Lecture Time
09:00 - 09:00
Speakers
  • Indunil Weerasena (Perth, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Aromatase inhibitor (AI) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combination is standard first line treatment for HR+/ HER2- metastatic breast cancer (MBC), providing improved progression-free survival (PFS) over AI alone. The combination therapy may delay anti-estrogen resistance including through clonal selection, phenotypic changes and new mutations. We hypothesized that limited progressive disease (LPD) would be more common on combination therapy driven by new mutations at limited site(s), in comparison to more generalized progressive disease (GPD) which would be more common on AI alone due to phenotypic cellular changes across broader sites. Confirmation would indicate that biopsy of progressive sites should be considered for duel-therapy PD and that loco-regional treatment (LRT) options could be explored more frequently for these cases.

Methods

Disease progression (PD) patterns on combined treatment were compared in patients treated in first-line setting for HR+/HER2- MBC. Progressing duel-treated patients (n=16) were compared to historic AI-only treated controls (n=32), matched 1:2 by age and adjuvant therapy. Mode of progression was classified as general (PD in the majority of lesions) or limited (PD in up to two lesions in a single organ). All LPDs were assessed for suitability for LRT at PD.

Results

LPDs were observed in 8 of 16 (50%) patients in the combination group and 4 of 32 (12.5%) in the AI group (p = 0.01). 10 of 12 cases (83%) with LPD were assessed as amenable for LRT. The sites of progression in these ten cases included six in bone, three affecting contralateral breast/chest wall and one in liver. Analysis of time to and mode of second relapse as well as overall survival (OS) for LPDs v GPDs await longer follow-up.

Conclusions

Combined CDK4/6i with AI treated patients in first line HR+/HER- MBC are more likely to develop LPD, where local therapy could be considered with no change to systemic therapy. In contrast general PD was more commonly observed in patients treated with AI alone, warranting change in systemic therapy.

Legal entity responsible for the study

A/Prof. Andrew Redfern, Dr Indunil Weerasena.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

54P - Platinum-based chemotherapy in advanced breast cancer (ABC): Real-world outcome from a tertiary cancer centre in India (ID 990)

Presentation Number
54P
Lecture Time
09:00 - 09:00
Speakers
  • Indhuja Vijesh (Chennai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There is a paucity of studies on platinum-based chemotherapy in advanced breast cancer (ABC) from developing countries like India.

Methods

This was a retrospective study of patients with ABC who were treated with platinum-based chemotherapy (gemcitabine carboplatin, GC) in a tertiary cancer center in India from Aug 2015 to Nov 2019. Patients were treated with injection gemcitabine 1gm/m2 on D1/D8 and injection carboplatin (AUC 5-6) on D1 for 6 cycles. Patients were assessed clinically before each cycle and by imaging before 4th and after the 6th cycle. Descriptive statistics were used to analyze the baseline characteristics. Survival was estimated with Kaplan Meier’s curve & univariate/multivariate analysis was done using regression analysis.

Results

Baseline characteristics are listed in the table. 34 % & 91 % had metastatic disease at initial presentation and at the start of GC respectively. Repeat biopsy at metastatic disease was done in 37 % & 50 % had the same molecular subtype. Median number of prior lines of systemic therapy for metastatic/progressive disease was 1 (range: 0 to 5). The median number of sites of metastasis was 2 (range: 0 to 6). Patients with visceral crises were 23%. The median number of cycles of GC chemotherapy received was 6 (range: 2 to 6). A dose reduction of chemotherapy was done in 74%.Only 57% patients could complete 6 cycles of chemotherapy. The responses among 34 evaluable patients were complete response (11%), partial response (23%), stable disease (40%) and progressive disease (23%). The hematological toxicities of all grade were seen in 91%, and 68% had grade 3 or 4 hematological toxicity. The median progression-free survival (PFS) and overall survival (OS) was 6 months [95% CI: 3.2-5.7 months] and 8 months [95% CI: 5.3-10.7 months] respectively. The 1-year PFS and OS were 19 % and 34% respectively. Univariate analysis did not show molecular subtype & BRCA status as a significant factor in improving PFS.The number of cycles of GC chemotherapy received ( >/= 3 cycles ) and the Infiltrating Ductal carcinoma histology ( IDC ) was significant in improving PFS, ( HR – 2.4, 95 % CI -1.04-5.67, p value – 0.04 ) & ( HR – 3.23, 95 % CI – 1.47 – 7.06, p value -0.03 ) respectively.

Baseline characteristics

Variable n (%)
Age Mean - 45.5 yrs; (28 – 68 yrs)
Sex Female- 34 (97%) Male- 1 (3 %)
Menopausal Status Premenopausal – 26 ( 75 %) Postmenopausal – 8 (23 %)
ECOG PS 1- 29 (83 % ) 2– 6 (17% )
Histology IDC- 27 (77 % ) Mixed – 6 (17% ) Others - 2 (6 % ) *
Grade Grade III -29 ( 83% ) Grade II – 6 (17% )
Hormone Receptor Status Low ER Positive -7 (20 % ) High ER positive- 6 (17% ) ER negative -22 (63 % ) Low PR positive - 5 (14 % ) High PR positive -3 (9 % ) PR negative- 27( 77 % )
Her 2 neu Positive – 6 (17%) Negative –28 (80 % ) Equivocal-1(3 % )
BRCA BRCA 1 – 6 ( 17% ) Negative – 6(17 % ) Not tested – 23 (66% )
Molecular Subtypes Luminal B -13 ( 37% ) Her 2 enriched -3 ( 9 % ) TNBC -19 ( 54% )

* 1 metaplastic, 1 Poorly differentiated with neuroendocrine features

Conclusions

This is the largest study from India on platinum-based chemotherapy in ABC. The real-world outcomes with platinum-based chemotherapy in ABC were PFS 6 months and OS 8 months. On multivariate analysis, patients who completed more than 3 cycles of GC chemotherapy had better survival (p value – 0.003, HR – 3.23, 95 % CI, 1.47 -7.06).

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

55P - Eribulin in heavily pretreated metastatic breast cancer: A real-world data from India (ID 1023)

Presentation Number
55P
Lecture Time
09:00 - 09:00
Speakers
  • Tanmoy K. Mandal (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Treatment of heavily pre-treated metastatic breast cancer (MBC) involves several lines of chemotherapy however, favourable side effect profile and a convenient mode of administration are important. Eribulin, is with proven activity in aggressive MBC however, there is paucity of real-world data from India and merits exploration.

Methods

We retrospectively analyzed, previously treated MBC patients who had at least 2 lines of prior therapy and received intravenous Eribulin at the dose of 1.4 mg/m2 on day 1 and 8 in 3 weekly cycles, between 2013 and 2019. To describe the clinical performance of eribulin we adopted the approach suggested by Dzimitrowicz and colleagues (J Clin Oncol. 2016; 34:3511e17); Tumour Response (TR) was defined as the proportion of physician-reported clinical or imaging (RECIST) response. Furthermore, we evaluated median Progression Free (PFS) and Overall Survival (OS) by the Kaplan Meier method. The patients were monitored for toxicity by CTCAE 4.3 criteria.

Results

There were 78 patients with the median age of 53 (32-75) years, 2 (2.6%) had male breast cancer. The median number of previous chemotherapy lines was 5(2-7); visceral involvement was present in 76 (97.4%) patients with median of 3 organs (range 0-6) involvement and bones (61.5%) being most common site followed by lung (52.5%). A median of 3.5 (1-11) cycles of eribulin was administered. TR seen as partial responses in 35 (44.9%), stable disease in 9 (11.5%), and progressive disease in 34 (43.6%) patients. The median PFS was 3.0 months (95% CI: 2.2-3.8), and median OS was 7 (95% CI: 5.1-8.9) months. Interestingly, eribulin activity was unrelated to the number of previous lines and type of metastatic involvement. Eribulin was well tolerated with only 2 (2.5%) patients discontinuing therapy due to toxicity. Significant grade 3/4 toxicities seen included peripheral neuropathy in 10 (12.8%) which peaked after 6 cycles and neutropenia in 17 (21.8%) of patients while dose reductions were required in 6 (7.7%) of patients.

Conclusions

In this relatively large, single Institution, real practice analysis eribulin is an efficacious, safe and easy to administer option for pre-treated MBC and merits consideration.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

56P - Treatment of palbociclib in hormone receptor-positive breast cancer in China: A real-world study (ID 876)

Presentation Number
56P
Lecture Time
09:00 - 09:00
Speakers
  • Yiqi Yang (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Palbociclib has been the first and only CDK4/6 inhibitor approved for breast cancer treatment by China Food and Drug Administration since July 2018. This research concluded the clinical use of palbociclib and provided stratified analyses by indicators that have not been reported, such as weight, percentage of estrogen receptor (ER) plus progesterone receptor (PR), and time to re-biopsy.

Methods

We retrospectively analyzed data from breast cancer patients treated with palbociclib and endocrine therapy from our medical center between May 2018 and January 2020.

Results

Among 51 patients treated with palbociclib, 14 patients were treated in first-line and 37 patients in second or later lines with a median progression-free survival (PFS) of 8 months (95% CI: 5.05-10.96), while the median PFS of first-line patients has not reached. Median PFS of all groups was 10 months (95%CI: 7-13). Patients with recent immunohistochemical confirmation 6 months before had a median PFS of 8 months (95% CI: 5.24-10.79) and group with pathology in 6 months had not reached its mPFS. Non-hepatic metastatic patients had a median PFS of 11 months (95% CI: 9.00-13.00), while the hepatic metastatic ones of 3 months (95% CI: 0.95-5.05). The objective response rate (ORR) was 10.6% (5/47, 95% confidence interval [CI]: 3.5%-23.1%) and clinical benefit rate (CBR) was 67.4% (29/43, 95% CI: 51.5%-80.9%). Better clinical outcomes were associated with recent pathological confirmation of immunohistochemical analysis (P=0.046) and non-hepatic metastasis (P=0.001), but they were not related to ER/PR percentage, Ki67 index, weight, or previous chemotherapy in first/second line of palbociclib setting groups.

Conclusions

Our report indicated favorable efficacy of palbociclib in terms of recent pathological confirmation and non-hepatic metastasis, providing further information about the use of palbociclib.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

57P - Therapeutic vulnerability of malignant phyllodes tumour to pazopanib identified through a novel patient-derived xenograft and cell line model (ID 599)

Presentation Number
57P
Lecture Time
09:00 - 09:00
Speakers
  • Dave Y. Ng (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Phyllodes tumours (PT) are rare fibroepithelial neoplasms accounting for less than 1% of all breast tumours in Western countries and up to 7% amongst Asian populations. Currently, no established standard therapy exists for malignant PT, an aggressive chemoresistant subtype with high metastatic potential. We hypothesized that patient-derived xenograft (PDX) and cell line models created in “real-time” may identify effective therapies to mirror a patient’s treatment trajectory.

Methods

Malignant PT from a chest wall mass was subcutaneously inoculated onto female NSG™ mice with serial transplantation to establish a PDX and cell line model (designated MPT-S1). In vitro cell viability and cell cycle analyses were performed following drug exposures.

Results

The affected patient was diagnosed with metastatic malignant PT affecting the chest wall and lungs. Histology of the chest wall mass showed a high grade malignant tumour composed of markedly pleomorphic spindle cells, interspersed with osteoclast-like multinucleated giant cells. On immunohistochemistry, tumour cells were positive for p63, negative for MNF116 and showed high proliferative index on Ki-67. Whole exome sequencing followed by Sanger sequencing confirmed mutations in TP53, PRB, MED12 and KMT2D. Immunohistochemistry and genomic profiles of the patient’s tumour, PDX, and cell line were consistent. Interestingly, despite primary resistance to conventional chemotherapies including doxorubicin, gemcitabine and docetaxel, the patient achieved partial response to off-label treatment with pazopanib, a multi-targeted receptor tyrosine kinase inhibitor (TKI). Correspondingly, drug susceptibility testing in vitro showed that pazopanib reduced cell viability in a dose-dependent manner (IC50 6.37 μM), accompanied by induction of S-phase arrest and apoptosis. Other TKIs including sorafenib, sunitinib and axitinib elicited similar effects (all IC50 <5 μM).

Conclusions

We established MPT-S1, a new PDX and cell line model of malignant PT, and provided initial evidence for the clinical utility of such models for identifying therapeutic vulnerabilities of rare cancers in real-time.

Legal entity responsible for the study

The authors.

Funding

SingHealth, Duke-NUS.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

58P - Survival benefit of local treatments in breast cancer with lung metastasis: Results from a large retrospective study (ID 971)

Presentation Number
58P
Lecture Time
09:00 - 09:00
Speakers
  • Yimeng Chen (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Systemic therapy is the standard treatment for metastatic breast cancer. However, there has been growing interest in the use of metastasis-directed therapy in selected cases. We investigated the role of local treatments in prolonging survival for lung-only metastases (LM) from breast cancer after mastectomy. Systemic therapy is the standard treatment for metastatic breast cancer. However, there has been growing interest in the use of metastasis-directed therapy in selected cases. We investigated the role of local treatments in prolonging survival for lung-only metastases (LM) from breast cancer after mastectomy.

Methods

Medical records of breast cancer with LM with available clinical data at National Cancer Center in China between 2003 and 2019 were screened. Breast cancer patients with LM receiving local therapy + pharmacotherapy (LPT, n=110) or pharmacotherapy (PT, n=287) were included. Their clinicopathologic characteristics and prognosis were analyzed retrospectively.

Results

After screening a series of medical records of 3785 patients with metastatic breast cancer, 387 were confirmed as initial isolate LM. Patients receiving LPT had significantly longer median overall survival (OS) than those treated with PT: OS 78.9 months versus 53.2 months (P=0.009), respectively. The 3-, 5- and 10-year survival rates for LPT group were 78.3, 58.3 and 25.3%, and those for PT group were 61.8, 42.3 and 20.3% (P = 0.01), respectively. Cox multivariate analysis confirmed the survival benefit induced by LPT. Estrogen receptor (ER)-negative of the primary tumour, ki67>20%, disease-free interval from surgery to LM≤24 months, LM-associated symptoms, and patients receiving systemic pharmacotherapy only were independently associated with poor prognosis.

Conclusions

Adding local therapy to systemic pharmacotherapy might prolong survival for lung metastases in breast cancer. Well-designed randomised clinical trials are warranted in the future.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

59P - The impact of site of metastasis on overall survival in indigenous and non-indigenous patients of Western Australia with breast cancer (ID 997)

Presentation Number
59P
Lecture Time
09:00 - 09:00
Speakers
  • Azim Khan (Nedlands, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Indigenous women with breast cancer (BrCa) have markedly higher mortality then non-Indigenous women. Here, we examine the impact of site of metastasis on overall survival (OS) in women with breast cancer by indigenous status.

Methods

We retrospectively examined data from WA cancer registry from 2001 to 2016 with metastatic BrCa by indigenous status. Cases with confirmed location of metastatic disease were analysed and divided into groups of bone, liver, brain, lung, gastrointestinal (GI)/genitourinary (GU), contralateral breast (CBr) and skin metastasis. We performed a univariate and linear regression analysis to determine the impact of metastasis site on OS. Kaplan-Meier, Chi-square, Mann-Whitney analysis were done.

Results

A total of 152 patients were studied, 39% (n=60) were indigenous vs 61% (n=92) non-indigenous. Inferior median OS for indigenous group 34 vs 51 months in non-indigenous group, p=0.015. Indigenous group had higher rates of metastasis to bone 61% vs 40% (p=0.014), lung 41% v 25% (p=0.031), liver 41% v 23% (p=0.021) when compared to non-indigenous patients. The GI/GU metastasis was higher in non-indigenous group 32% v 15% (p=0.015) in indigenous group. There were no significant differences in rate of relapse at the local, CBr, brain, spleen, non-axillary LN nor skin (p>0.05). The bone metastasis was most common in luminals, liver and lung metastasis were frequent in luminal B and Her2+ subtypes. Brain metastasis was most frequent in HER2+. Indigenous cohort had more HER2+, luminal B and TN’s than non-indigenous but this was non-significant, p < 0.467. The multiple linear regression in both groups to predict OS for site-specific metastasis was non-significant with p-value 0.067 and R2 of 0.097, explaining slight variability of OS by sites of metastasis. After adjustment, only brain metastasis had significant regression weights, but further analysis shown non-significant effect on OS with p=0.072 and an R2 of 0.021.The group with brain metastasis had OS of 38 vs 52 months with no brain metastasis, p=0.072.

Conclusions

The indigenous group had inferior survival and higher rates of relapse to bones and viscera. A larger prospective study is needed to establish links of site of metastasis and OS.

Legal entity responsible for the study

Dr Azim Khan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

60P - Risk factors of bone metastasis and skeletal-related events in high-risk breast cancer patients (ID 407)

Presentation Number
60P
Lecture Time
09:00 - 09:00
Speakers
  • Sumadi Lukman Anwar (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The bone is the most common site of distant metastasis from breast cancer that predisposes the patients for skeletal-related events (SREs) and often causes severe morbidity and poor quality of life. Identification of predilections and risk factors associated with bone metastasis and SREs is important in planning (neo)adjuvant treatment and surveillance systems particularly in a population of patients diagnosed in late stages such as in Indonesia and other developing countries.

Methods

Clinicopathological variables of breast cancer with intermediate to the high-high risk of recurrence were collected from a dataset in the Dr Sardjito Hospital, Indonesia. Risk factors affecting bone metastasis and SRE were then analyzed.

Results

Of 1081 non-metastatic breast cancer patients diagnosed from 2013 through 2018, 129 patients (11.9%) developed bone metastasis during a median follow up of 4.4 years. SREs occurred in 89 (68.5%) patients. In multivariable analysis, positive axillary lymph nodes (OR 2.189, p=0.002), early menopause (OR 2.020, p=0.030), luminal subtype (OR 1.811, p=0.003), advanced stage (OR 1.869, p=0.004), and having multiple metabolic comorbidities (OR 1.992, p=0.004) were significantly associated with risk of skeletal metastasis. Only positive lymph nodes, luminal subtype, and advanced stages were associated with higher SREs. Of 102 (82.2%) and 52 (40.3%) patients received bone-modifying agents and external radiotherapy, respectively.

Conclusions

The rates of bone metastasis and SREs are relatively high in breast cancer patients diagnosed in advanced stages. Our study suggests the importance of considering patients with high-risk of SREs and the need of treatment advancement to further prevent SREs in the care of breast cancer with bone metastasis.

Legal entity responsible for the study

Sumadi Lukman Anwar.

Funding

Universitas Gadjah Mada.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

61P - Clinical implication of BRCA mutation in breast cancer with central nervous system metastasis (ID 525)

Presentation Number
61P
Lecture Time
09:00 - 09:00
Speakers
  • Jwa Hoon Kim (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Clinical implication of BRCA mutation in patients with breast cancer (BC) with central nervous system (CNS) metastasis is unclear.

Methods

Data of 2,883 patients with BC who underwent BRCA1/2 mutation test at Asan Medical Center between 2011 and 2018 were reviewed. Clinical characteristics and outcomes were compared according to the presence of BRCA1/2 mutation in patients with BC with CNS metastasis.

Results

Among 2,883 patients, 82 patients developed CNS metastasis: 29 of 696 (4.2%) in BRCA1/2 mutation carriers and 53 of 2,187 (2.4%) in non-BRCA mutation carriers. Median age at CNS metastasis was 41 yrs (range 27-76). The proportion of BC subtypes was different according to the presence of BRCA1/2 mutation: hormone receptor (HR) (+) and HER2 (-) (41.4% vs. 24.5%, P=0.113) and HER2 (+) regardless of HR (6.9% vs. 32.1%, P=0.013) between BRCA1/2 mutation and non-BRCA mutation carriers, while no difference was observed regarding triple-negative BC (TNBC) (51.7% vs. 43.4%) (P=0.470). Among patients with BRCA1/2 mutation, most of the BRCA1 mutation carriers had TNBC (77.8%), whereas most of BRCA2 mutation carriers had HR+ BC (60%) (P=0.060). Median time to CNS metastasis from metastatic BC was 1.1 yrs (95% confidence interval 0.74-1.41) without difference between BRCA1/2 and non-BRCA mutation carriers. BRCA1 carriers significantly develop CNS metastasis earlier than BRCA2 mutation carriers (0.8 vs. 1.6 yrs, P=0.015). Patterns of CNS metastasis were similar by presence of BRCA1/2 mutation: brain parenchymal metastasis (BM) alone (62.1% vs. 73.6%), leptomeningeal metastasis alone (10.3% vs. 9.4%), and both (27.6% vs. 17%). There were no differences in isolated CNS metastasis, single or multiple BM, and uncontrolled CNS metastasis rates with similar treatment of CNS metastasis. At a median follow-up of 24.5 months, median overall survival from CNS metastasis in BRCA1/2 mutation carriers seemed to be shorter than in non-BRCA mutation carriers (6.0 vs. 8.9 months, P=0.284).

Conclusions

CNS involvement is frequent in BRCA1/2 mutated BC and BC subtypes were different according to the presence of BRCA1/2 mutation in patients with BC with CNS metastasis. BRCA1 carriers developed CNS metastasis earlier and may be associated with poor survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

62P - IGF axis in breast cancer recurrence and metastasis (ID 1014)

Presentation Number
62P
Lecture Time
09:00 - 09:00
Speakers
  • Hajara Akhter (Dhaka, Bangladesh)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) are the major components in the IGF axis that play an important role in the development and progression of cancer. However, little is known about the circulatory levels of these proteins with recurrence and metastasis in breast carcinoma (BC).

Methods

One hundred and twenty-eight (128) breast cancer patients who underwent mastectomy were purposively taken from a prospective study. Clinicopathological information was collected from patients’ medical records. Anthropometric and biochemical parameters were measured by standard methods. Growth and metabolic factors were estimated by enzyme-linked immunosorbent assay (ELISA), and compared for patients’ recurrence and metastasis.

Results

The mean age at diagnosis was 44 years. Most of the tumors (94%) were ductal cell carcinoma. Two thirds were moderately differentiated tumor grade and lymph node positive [70% and 67% respectively]. Circulatory levels of IGFBP1 were significantly higher (p<0.05) in patients who received adjuvant chemotherapy; and patients with recurrence and metastasis while IGF1 was found to be significantly increased in only metastatic breast cancer (p<0.05). IGFBP-1 levels were correlated with SGPT, ALP, hemoglobin, WBC, ESR, CA15.3 and contraceptive use, whereas, IGF-1 was associated with insulin, HOMA %B and ESR.

Conclusions

High serum levels of IGFBP-1 and IGF-1 may be associated with breast cancer recurrence and metastasis. These results need to be confirmed in larger breast cancer survivor cohorts.

Legal entity responsible for the study

TWAS, Ministry of Education (MoE) Bangladesh.

Funding

The World Academy of Sciences (TWAS), Trieste, Italy. Bangladesh Bureau of Educational Information & Statistics (BANBEIS), Ministry of Education (MoE), Dhaka, Bangladesh.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

63P - Butterfly pea (Clitoria ternatea Linn.) flower extract prevents MCF-7 HER2-positive breast cancer cell metastasis in-vitro (ID 676)

Presentation Number
63P
Lecture Time
09:00 - 09:00
Speakers
  • Azzahra -. Asysyifa (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is one of the cancers with highest incidence with more than two million people diagnosed in 2018 and causes more than 600.000 deaths. The big number of deaths are mostly due to breast cancer metastasis. Butterfly pea flower (Clitoria ternatea Linn.) is a medicinal plant which is known to have a wide range of pharmacological activities because it contains many kinds of active substances one of which is quercetin known to have anti-breast cancer activity especially metastasis through inhibition of NF-κB (nuclear factor kappa B). Those transcription factors play an important role in the metastasis process in HER2-positive breast cancer type. The butterfly pea flower activity as an antimetastatic agent in MCF-7 HER2-positive has not been well understood. The aim of the study was to find out the antimetastatic activity of butterfly pea flower extract on MCF-7 HER-positive breast cancer cell line.

Methods

Maceration process using 96% ethanol to obtain the crude extract, thin layer chromatography (TLC) to see the phytochemical profile of butterfly pea leaf extract, MTT assay to determine the IC50 using log probit analysis as a reference for the next test which is scratch wound healing assay to assess the effect of butterfly pea leaf extract on the migration of 4T1 breast cancer cell line.

Results

Butterfly pea flower extraction using maceration obtains a 18.06% yield. Phytochemical study using thin layer chromatography suggested the Rf of crude extract had the same Rf with quercetin standard which is 0.57 so it was proven that the crude extract contained quercetin. The MTT assay and log probit analysis showed the IC50 of butterfly pea crude extract was 862 μg/mL. The scratch wound healing assay using concentrations below IC50 showed 50% of cell migration activity of the MCF-7 HER2-positive was inhibited in 24 hours interval by 380 μg/mL crude extract and in 48 hours interval with 500 μg/mL of crude extract was able to prevent the scratch closure. Statistical analysis using SPSS 16.0 showed that the crude extract can significantly suppressed the migration of the cancer cell.

Conclusions

Butterfly pea flower extract has an antimetastatic activity to MCF-7 HER2-positive breast cancer cell line in-vitro.

Legal entity responsible for the study

The authors.

Funding

UGM.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

64P - Pre-treatment absolute white blood cell profile count as metastatic predictive factors in invasive ductal carcinoma breast cancer (ID 815)

Presentation Number
64P
Lecture Time
09:00 - 09:00
Speakers
  • Wikania W. I Gede (Denpasar, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Metastasis is the one main causes of mortality in solid cancers, including breast cancer recently predictive biomarkers based on molecular finding have been developed but still unaffordable especially in developing countries. There are several alternative to molecular biomarkers and white blood cell profile count emerged as affordable and practical markers of cancer progression. However, there are not many studies that focus on their direct application. Therefore, this study aimed to determine the correlation between white blood cell profile count as predictive factors of metastasis in invasive ductal carcinoma breast cancer.

Methods

A retrospective cross-sectional study was conducted using breast cancer patient data obtained at Sanglah General Hospital (2016-2020). Complete blood count (CBC) and histopathological records of the patients were collected and the white blood cell profile (WBC, ABC, AMC, AEC, ANC and ALC) were calculated. Distant metastasis was classified into M0 and M1.

Results

267 invasive ductal carcinoma breast cancer patient data were used in this study with mean age 49.1 ± 9.474. Metastatic disease of the patients accounted for 50 patients (18.7%) of all patients. Patients with metastatic disease had higher median of AMC compared to patients without metastasis (0.61 ± 0.307, p=0.022. The AUC (sensitivity and specificity) of ABC, AMC and ANC in predicting metastasis were 0.528 (24%; 90%), 0.604 (56%; 72%) and 0.539 (40%; 74%), respectively. In univariate risk analysis model, patient with metastasis of invasive ductal carcinoma breast cancer was found in high ABC (OR: 2.779; 95%CI=1.277-6.134; p=0.008), AMC (OR: 1.203; 95%CI=0.661-2.189; p<0.001) and ANC (OR: 1.917; 95%CI=1.008-3.643; p=0.045).

Conclusions

Pre-treatment white blood cell profile count are potential predictive markers for metastasis. However, these findings need to be validated in larger study with more comprehensive design.

Legal entity responsible for the study

Medical Faculty Udayana University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

65P - The new mouse anti-nNav1.5 monoclonal antibody (ID 954)

Presentation Number
65P
Lecture Time
09:00 - 09:00
Speakers
  • Nur Aishah Sharudin (Kubang Kerian, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Neonatal Nav1.5 (nNav1.5) is a potent tumour metastatic marker found re-expressed in human breast cancer cells with aggressive phenotype and breast tumour tissue positive for lymph node metastasis. Mouse anti-nNav1.5 monoclonal antibody, 4H8 was recently obtained.Neonatal Nav1.5 (nNav1.5) is a potent tumour metastatic marker found re-expressed in human breast cancer cells with aggressive phenotype and breast tumour tissue positive for lymph node metastasis. Mouse anti-nNav1.5 monoclonal antibody, 4H8 was recently obtained. This study aimed to assess the specificity of the 4H8 against nNav1.5.

Methods

4H8 was used as primary antibody in Western blot and immunocytochemistry tested on cells and cell lysates, respectively of two human breast cancer cell line; MDA-MB-231+nNav1.5 and MCF-7-nNav1.5, a mouse mammary cancer cell line, 4T1+nNav1.5, a non-cancerous human breast epithelial, MCF-10A-nNav1.5 and tumour tissue lysate from an orthotopic syngeneic mouse model (4T1+nNav1.5/BALB/c).

Results

were consistent with nNav1.5 protein being more abundantly expressed in aggressive human breast cancer cell line, MDA-MB-231+nNav1.5 and mouse mammary cancer cell line, 4T1+nNav1.5 and tumour tissue lysate from an orthotopic syngeneic mouse model (4T1+nNav1.5/BALB/c) as compared to MCF-7-nNav1.5 and MCF-10A-nNav1.5.

Conclusions

The new antibody described in this work can be a novel tool in studying nNav1.5 expression in breast cancer.

Legal entity responsible for the study

Institute of Research for Molecular Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

66P - The TILs near solid structures is a potential prognostic factor of distant metastases in the luminal HER2-negative breast cancer (ID 973)

Presentation Number
66P
Lecture Time
09:00 - 09:00
Speakers
  • Vladimir V. Alifanov (Tomsk, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The phenomenon of intratumoral morphological heterogeneity is associated with both the progression of the disease and chemosensitivity and chemoresistance. However, there are very few data about the microenvironment heterogeneity near morphological structures in breast cancer patients of various molecular subtypes. This phenomenon may underlie the failure of tumor-infiltration lymphocytes as a prognostic factor in luminal forms of breast cancer.

Methods

152 patients with IC NST (T1–3N0–2M0) aged 29 to 75 years were enrolled in the study. The molecular subtype was determined using immunohistochemical analysis of the expression of estrogen and progesterone receptors, Ki-67 and Her2/neu. TILs were assessed in accordance with the recommendations of the International TILs Working Group

Results

It was shown that TILs near the various morphological structures is heterogeneous only in luminal Her2-negative patients. In addition, was found that the development of distant metastases and worse metastatic-free survival in this cohort of patients is associated with a high (more than 5%) TILs near solid structures and also depended on Ki-67 level.

Conclusions

TILs near solid structures is a potential prognostic factor for the development of distant metastasis in the luminal Her2-negative and Ki-67 level less 20% subtype of IC NST. The study was supported by the Russian Science Foundation (grant #20-75-10033).

Legal entity responsible for the study

The authors.

Funding

the Russian Science Foundation.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

67TiP - HER2CLIMB-02: A randomized, double-blind, phase III study of tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer (ID 283)

Presentation Number
67TiP
Lecture Time
09:00 - 09:00
Speakers
  • Norikazu Masuda (Osaka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tucatinib (TUC), an oral tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR, is approved in the US for use in combination with trastuzumab (Tras) and capecitabine for treatment (tx) of patients (pts) with metastatic HER2+ breast cancer (MBC), including pts with brain metastases (BM), who received 1 or more prior anti-HER2-based regimens in the metastatic setting. Ado-Tras emtansine (T-DM1), approved for tx of HER2+ MBC after Tras and a taxane, has improved progression-free survival (PFS) and overall survival (OS). Improvements are needed, including pts with active BM. A phase Ib trial evaluated TUC (300 mg PO BID) with T-DM1 in 50 pts with HER2+ MBC who received prior tx with Tras and a taxane; 60% of pts had BM at baseline (Borges 2018). Common AEs, mostly grade 1/2, were nausea (72%), diarrhea (60%), and fatigue (56%). Median PFS was 8.2 months and objective response rate (ORR) in pts with measurable disease (n=34) was 47%. Brain specific response rate (RECISTv1.1) in pts with measurable BM (n=14) was 36%. This encouraging clinical activity, including in pts with BM, provides rationale to evaluate this combination.

Trial design

HER2CLIMB-02 is a global, randomized, double-blind, placebo-controlled, phase III study enrolling pts with centrally confirmed HER2+, unresectable, locally advanced, or MBC previously treated with Tras and taxane (in any setting), and ECOG ≤1. ∼460 pts will be randomized 1:1 for 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV). Prior tx with investigational anti-HER2 or anti-EGFR agent or HER2 TKI is not permitted. Prior pertuzumab tx is permitted. Baseline brain MRIs are required; pts with stable, progressing, or untreated BM not requiring immediate local therapy are eligible. On tx response assessments per RECISTv1.1 occur every 6 wks for the 1st 24 wks, and then every 9 wks. Primary endpoint is PFS per investigator assessment, with OS and ORR as key secondary endpoints. Enrollment is ongoing in North America, EU, and will include Japan, South Korea, Singapore, and Australia.

Clinical trial identification

NCT03975647; 2019-005017-39.

Legal entity responsible for the study

Seattle Genetics, Inc.

Funding

Seattle Genetics, Inc.

Disclosure

N. Masuda: Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli-Lilly; Honoraria (self): Takeda; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Daiichi Sankyo; Full/Part-time employment: National Hospital Organization Osaka National Hospital, Dept. of Surgery, Breast Oncology; Officer/Board of Directors: Japan Breast Cancer Research Group Association Board of Directors. S. Hurvitz: Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): OBI Pharma; Advisory/Consultancy, Research grant/Funding (institution), medical writing: Pfizer; Research grant/Funding (institution): Pieris Pharma; Research grant/Funding (institution): Puma Biotech; Research grant/Funding (institution): Radius Health; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, medical writing: Roche; Research grant/Funding (institution): Bayer. L. Vahdat: Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics, Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Polyphor; Advisory/Consultancy: Berg Pharma; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Other: Roche; Research grant/Funding (institution), Other: Arvinas; Research grant/Funding (institution): Polyphor; Research grant/Funding (institution): Oncotherapy Biosciences; Licensing/Royalties, A patent on bone marrow derived progenitor and relapse: No company. N. Harbeck: Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics, Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Officer/Board of Directors: West German Study Group. A.C. Wolff: Full/Part-time employment: John Hopkins Kimmel Cancer Center, Breast and Ovarian Cancer Program. S.M. Tolaney: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celldex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Nanostring; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Paxman; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics, Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Odonate; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics; Honoraria (self), Advisory/Consultancy: G1 Therapeutics; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Anthenex; Honoraria (self), Advisory/Consultancy: Oncopep; Honoraria (self), Advisory/Consultancy: Kyowa Kirin Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Daiichi-Sankyo; Research grant/Funding (institution): Exelixis. S. Loi: Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Novartis; Advisory/Consultancy: GlaxosmithKline; Advisory/Consultancy: G1 Therapeutics; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Bristol-Meyers Squibb; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Merck; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Roche-Genentech; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Pfizer; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics, Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. J. O'Shaughnessy: Honoraria (self): AbbVie; Honoraria (self): Agendia; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi-Sankyo; Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genomic Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Grail; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Heron; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Immunomedics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ispen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Jounce; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Myriad; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Odonate Therapeutics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma Biotech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Samsung; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics, Inc.; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Syndax; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi. D. Xie: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics, Inc.; Shareholder/Stockholder/Stock options: Metlife. L. Walker: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Seattle Genetics, Inc.. E. Rustia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics, Inc.. V.F. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics, Inc.; Research grant/Funding (self): Abbot/AbbVie; Research grant/Funding (institution): Millenium.

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e-Poster Display Session (ID 87) Poster Display

68TiP - KEYLYNK-009: A phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (ID 515)

Presentation Number
68TiP
Lecture Time
09:00 - 09:00
Speakers
  • Shigehira Saji (Fukushima, Fukushima, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immunotherapy + chemotherapy (chemo) is a promising approach for 1L treatment of locally recurrent, inoperable TNBC or metastatic TNBC (mTNBC). An unmet need exists for effective and tolerable maintenance regimens in mTNBC to sustain clinical benefit after induction therapy and avoid potential toxicity or resistance to prolonged chemo. The PARP inhibitor ola has shown efficacy as maintenance therapy for platinum-sensitive ovarian cancer. The high prevalence of BRCAm (or “BRCAness”) in TNBC may make these tumors sensitive to DNA-damaging agents. Moreover, evidence suggests that ola + PD-1 inhibitor pembro may provide greater clinical benefit than with either agent alone. KEYLYNK-009 (NCT04191135) is a phase II/III, open-label, randomized study of pembro + ola vs chemo after induction with 1L pembro + chemo in locally recurrent, inoperable TNBC or mTNBC.

Trial design

This 2-in-1 study will enroll ∼317 pts in phase II and ∼615 additional pts in phase III if a planned efficacy boundary is met. Pts eligible for induction therapy must have measurable, locally recurrent, inoperable TNBC that cannot be treated with curative intent or mTNBC previously untreated with chemo. Pts will receive up to 6 cycles of induction therapy with pembro 200 mg Q3W + chemo (carboplatin AUC 2 + gemcitabine 1000 mg/m2 on days 1 + 8 Q3W). Pts eligible for postinduction treatment must achieve CR or PR or maintain SD during induction after 4-6 treatment cycles, with ECOG PS 0/1 and no persistent grade >1 toxicities related to induction therapy (excluding alopecia, Hb ≥9.0 g/dL, grade 2 hyper-/hypothyroidism, or grade 2 hyperglycemia). These pts will be randomized 1:1 to pembro 200 mg Q3W + ola 300 mg BID or continue pembro + chemo (same as induction regimen) until completion of 35 cycles of pembro (including induction), progression, or unacceptable toxicity. Phase III primary endpoints are PFS (RECIST v1.1 by BICR) and OS. Secondary endpoints include OS and PFS in pts with BRCAm, HRQoL, and safety. Pt enrollment is ongoing and anticipated at 110 sites in 14 countries.

Clinical trial identification

NCT04191135.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

S. Saji: Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self): Daiichi Sankyo; Honoraria (self), Research grant/Funding (self): Eisai; Honoraria (self): Eli Lilly; Honoraria (self): Kyowa Kirin; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self): Takeda. A. Llombart Cussac: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Licensing/Royalties: MedSIR. F. Andre: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: GlaxoSmithKline. M.E. Robson: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca.; Advisory/Consultancy: Change Health Care; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): InVitae; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Non-remunerated activity/ies, Physician Education Resource; Research to Practice: Clinical Care Options; Non-remunerated activity/ies, Uncompensated Relationships: Daiichi Sankyo; Non-remunerated activity/ies, Uncompensated Relationships: Merck; Non-remunerated activity/ies, Uncompensated Relationships: Pfizer. N. Harbeck: Shareholder/Stockholder/Stock options: West German Study Group; Honoraria (self): Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Genomic Health; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Honoraria (self): Roche; Honoraria (self): Zodiac Pharma; Advisory/Consultancy: Agendia; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Advisory/Consultancy: Odonate Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: West German Study Group. P. Schmid: Research grant/Funding (institution), Full/Part-time employment: Genentech; Honoraria (self), Research grant/Funding (institution), Full/Part-time employment: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): Pfizer; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Honoraria (self): Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Puma Biotechnology; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Oncogenex. D.W. Cescon: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Agendia; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Licensing/Royalties, Patent Pending: Biomarkers of TTK inhibitors : University of Toronto. J.S. Ahn: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb-Ono Pharmaceutical; Honoraria (self): Eisai; Honoraria (self): Janssen; Honoraria (self): Menarini; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Roche; Advisory/Consultancy: Samsung Bioepis. R. Nanda: Advisory/Consultancy: Aduro; Advisory/Consultancy: Athenex; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Ionis; Advisory/Consultancy: Macrogenics; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Corcept Therapeutics; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Odonate Therapeutics; Non-remunerated activity/ies: G1 Therapeutics. L. Fan: Full/Part-time employment: li_fan2@merck.com. J.A. Mejia: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. V. Karantza: Shareholder/Stockholder/Stock options, Full/Part-time employment: erck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A. Bardia: Advisory/Consultancy: Biotheranostics Inc.; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: Phillips; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Radius Health; Advisory/Consultancy: Diiachi Pharma/AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Taiho. H.S. Rugo: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): OBI; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Odonate; Advisory/Consultancy: Puma; Advisory/Consultancy: Samsung.

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e-Poster Display Session (ID 87) Poster Display

69TiP - MADELINE Asia: A mobile app-based prospective observational study of patient reported outcomes in advanced breast cancer in Asia (ID 757)

Presentation Number
69TiP
Lecture Time
09:00 - 09:00
Speakers
  • Anna Y. Tai (Hong Kong, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The incidence of breast cancer in Asia is rising. Recent advances in hormone receptor (HR) positive and human epidermal growth factor receptor negative advanced breast cancer (aBC) includes introduction of the CDK 4/6 inhibitors. Palbociclib was the first drug in this class to be introduced in Asia and is approved for use in aBC in combination with aromatase inhibitors (P+AI) as initial endocrine based therapy in postmenopausal women or with fulvestrant (P+F) in women with disease progression following endocrine therapy. Globally, there has been evaluations in the real world setting for palbociclib. However, data published for Asian patients in this setting remains scarce.

Trial design

Study Design: A prospective, observational, non-interventional, multi-centre study. A smartphone-based mobile application to collect patient-reported outcomes (PROs) associated with aBC and its treatment on Palbociclib has been developed. The impact of aBC and associated treatment of symptoms, functioning and quality of life (QOL) as reported by patients will be studied. Clinical data on therapy management, occurrence of neutropenia and any association between neutropenia, quality of life and PROs will also be captured. Eligibility Criteria: Women with HR+/HER2– aBC receiving P+AI or P+F as per approved indication in their country. Aims and Objectives: Primary objectives are to assess and describe clinical and PROs in eligible patient population. 12-Item ‘Short Form Health Survey’ & ‘Center for Epidemiological Studies Depression Scale’ would be used. The study will also document changes in therapy as well as the incidence, severity, and duration of neutropenia through data recorded from patient’s medical records. Statistical Methods: For the purpose of this study, analyses will generally be descriptive in nature and will be conducted using SAS statistical software Present Accrual and Target Accrual: Approximately 100 patients from up to 12 sites within 4 Asian countries (Taiwan, India, Malaysia and Hong Kong) will be enrolled. Study duration will be approximately 12 months assuming 6 months of recruitment. The study is open in all 4 participating countries with 7 patients recruited so far.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

M. Singh, J. Binko, M. Alam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. K. Lilly, S. Chang: Full/Part-time employment: Parexel International Pty Ltd. S. Bowles: Full/Part-time employment: Intouch Solutions. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO5 - Response of an ERBB2 Exon 20 Insertion Mutation Breast Cancer to Pyrotinib (ID 1015)

Presentation Number
YO5
Lecture Time
09:00 - 09:00
Speakers
  • Fan Yang (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

Response of an ERBB2 Exon 20 Insertion Mutation Breast Cancer to Pyrotinib

Abstract

Breast cancer is the most frequent malignancy among women worldwide, the incidence of which is increasing at a high rate. With the advent of next-generation sequencing, a small proportion of relapsed and refractory breast cancers could be found to harbor activating somatic mutations, making them susceptible to anti-HER2 (human epidermal growth factor receptor 2) therapies. Here, we present a case of a breast cancer patient with ERBB2 (Erb-b2 receptor tyrosine kinase 2) exon 20 insertion mutation, treated successfully with pyrotinib plus trastuzumab combined with chemotherapy. We also confirmed that pyrotinib could inhibite MAPK/ERK pathway in ERBB2 mutation cells. This case also highlights the usefulness of genomic testing in patients, which may help to expand the therapeutic options available to them.

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e-Poster Display Session (ID 87) Poster Display

Developmental therapeutics (ID 1144)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

73P - Selinexor in combination with carboplatin and pemetrexed (CP) in patients with advanced or metastatic solid tumors: Results of an open label, single-center, multi-arm phase Ib study (ID 278)

Presentation Number
73P
Lecture Time
09:00 - 09:00
Speakers
  • Kyaw Z. Thein (Portland, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Exportin 1(XPO-1) is overexpressed in various tumors and selinexor is a first-in-class oral potent selective inhibitor of XPO-1, leading to intranuclear accumulation of tumor suppressor proteins. In vivo studies have suggested that selinexor in combination with various chemotherapeutics exerts antitumor activity in multiple cancers.

Methods

This was an open label, single-center, multi-arm phase Ib study utilizing a “3 + 3” design and a “basket type” expansion. CP + selinexor was employed as one of the 13 parallel arms. While carboplatin was dosed at AUC6 along with pemetrexed at 500 mg/m2 IV Q3W, selinexor was dosed at 60 mg twice weekly (BIW) or 40-60 mg once weekly (QW). Patients with advanced or metastatic solid tumors whose disease was refractory, had relapsed following prior systemic therapy or where the addition of selinexor to standard chemotherapy deemed appropriate and acceptable, were eligible.

Results

Six patients with the median age of 51 (range, 37–69 years) were treated, and 4 were evaluable for response. The cancer types were ovarian (n=2), and 1 each with thymoma, cervical, rectal, and non-small cell lung cancers. All patients had at least one treatment-emergent adverse events (TEAE) and the common TEAE were thrombocytopenia (6/6), neutropenia (5/6), fatigue (5/6), anemia (4/6), leukopenia (4/6), elevated AST or ALT (3/6), nausea (3/6), and vomiting (3/6). The most prevalent grade ≥3 TEAE were thrombocytopenia (4/6), anemia (3/6), neutropenia (3/6), leukopenia (2/6), and fatigue (2/6). A patient dosed at selinexor 40mg QW experienced DLT with grade 3 fatigue despite medical supportive care ≥5 days. The patient with lung adenocarcinoma who had 2 prior therapies including prior carbo-taxol achieved partial response (PR) whereas 2 patients with ovarian cancer and cervical cancer had stable disease (SD), contributing the clinical benefit rate (CR+PR+SD ≥4 months) of 50%.

Conclusions

Albeit the number of patients in this study arm was small, once weekly oral selinexor in combination with CP was plausible and conferred some clinical activity and disease stabilization. The RP2D of selinexor was 40 mg QW in combination with CP.

Clinical trial identification

NCT02419495.

Legal entity responsible for the study

The authors.

Funding

Karyopharm.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

74P - Comprehensive transcriptome analysis of endoplasmic reticulum stress in osteosarcomas (ID 932)

Presentation Number
74P
Lecture Time
09:00 - 09:00
Speakers
  • Yoshiyuki Suehara (Tokyo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Bone and soft-tissue sarcomas are rare malignant tumors comprising numerous histological subtypes. Novel effective therapies are still required. Recently, endoplasmic reticulum stress (ERs) responses have been suggested to be involved in the malignancy of various cancer types, prompting new studies focused on this area for the development of new therapies. Our previous proteomic study demonstrated an association between the ERs response and malignant behaviors in Ewing sarcomas (ESs). We also found that IRE1α inhibitors exert antitumor activity in ESs (Tanabe Y et al. Oncotarget 2017). To develop novel therapies for osteosarcomas (OSs), we performed comprehensive expression study of ERs genes using ER response arrays. Identified factors based on ER response arrays were investigated to elucidate these functional and antitumor activities using inhibitors of identified ERs in OSs.

Methods

To elucidate roles of main ER pathway in OS, we performed ER response arrays using OS cell lines. Based on results of ER response arrays, we conducted reverse transcription polymerase chain reaction (RT-PCR) and quantitative (q)-PCR to elucidate the expression of XBP1 and XBP1 splicing (XBP1s) variants in OS cell lines (143B, MG63, KHOS, KHOSR2, U2OS, U2OSR2) and surgical materials. Furthermore, we also performed XBP1 siRNA and inhibitor assays using several IRE1α-XBP1 inhibitors.

Results

ER response arrays using OS cell lines indicated some other pathways including XBP1 had high expressions in transcriptome levels. As we suggested XBP1played crucial roles in OS cell lines, we conducted functional assay focusing on XBP1 in OS cell lines. Expression of XBP1 was confirmed in OS cell lines and surgical materials by RT-PCR. The knockdown of XBP1 expression by siRNA inhibited the cell proliferation of the OS cell lines. Regarding inhibitor assays using IRE1α-XBP1 inhibitors, toyocamycin exerted a strong anti-tumor effect (IC50 <0.07 [0.04 to 0.07] μM) in the OS cell lines, despite SYO1, synovial sarcoma cell line had resistance of the inhibitor.

Conclusions

We found the association between the ER response and the tumor activity in OS. We also found that IRE1α-XBP1 inhibitors suppressed cell growths in OS.

Editorial acknowledgement

This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19H03789 and 19K22694 to Y.S.; 19K16753 to K.A.; 18K15329 to T.O.; # 18K16634 to Y.K.).

Legal entity responsible for the study

The authors.

Funding

This study was supported by Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number #19H03789 and 19K22694 to Y.S.; 19K16753 to K.A.; 18K15329 to T.O.; # 18K16634 to Y.K.).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

75P - The evaluation of selective sensitivity of EZH2 inhibitors based on synthetic lethality in ARID1A-deficient gastric cancer (ID 401)

Presentation Number
75P
Lecture Time
09:00 - 09:00
Speakers
  • Leo Yamada (Fukushima, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene and frequently mutated in gastric cancer (GC). Although ARID1A mutations are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach are effective for ARID1A-deficient cancers. EZH2, the histone methyltransferase and a member of the polycomb repressive complex 2 (PRC2), catalyzes the trimethylation of lysine 27 on histone 3 and showed a synthetic lethality in ARID1A-mutated ovarian cancer, but its role in GC has not been investigated yet.

Methods

The selective sensitivity of the EZH2 inhibitors for ARID1A-deficient GC cells was evaluated using cell viability and colony formation assays enrolling three kinds of EZH2 inhibitors. The expression of PI3K/AKT signaling genes was investigated using TCGA’s cBioPortal database to determine whether the homeostasis between ARID1A and EZH2 is related to cell proliferation and survival via the PI3K/AKT signaling pathway. We also evaluated the expression of EZH2, PD-L1, and PD-L2, MSI status, and EBV infection were investigated in ARID1A negative GC using patient samples.

Results

EZH2 inhibitors decreased the viability of ARID1A-deficient cells in a dose-dependent manner and demonstrated the selective sensitivity to ARID1A-deficient cells in vitro experiment system. A bioinformatics approach revealed that the PI3K/AKT signaling tended to be activated in ARID1A-deficient GC enhancing cell viability and, furthermore, down-regulation of EZH2 in ARID1A-deficient GC was related to normalization of PI3K/AKT signaling pathway. Clinicopathological characteristics of ARID1A negative GC with ARID1A, EZH2, PD-L1, and PD-L2 expressions, MSI, and EBV status were summarized.

Conclusions

The present findings provide a rationale for the selective sensitivity of EZH2 inhibitors against ARID1A-deficient GC and suggest the potential efficacy of targeted therapy using EZH2 inhibitors in this patient population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

76P - Targeted tumour photoImmunotherapy against triple-negative breast cancer therapy (ID 154)

Presentation Number
76P
Lecture Time
09:00 - 09:00
Speakers
  • Vivek Raju (Coimbatore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Triple-negative breast cancer (TNBC) is a breast cancer subtype. At present, TNBC patients do not have an approved targeted therapy. Therefore, patients primarily depend on forceful treatment of systemic chemotherapy that has inevitable adverse effects, shows poor therapeutic outcomes, leads to high mortality rates, and advanced stage of TNBC patients remains very high. Hence, there is a need to develop effective targeted therapies for the TNBC patient population. Emphasizing the new nanotherapeutic approach in TNBC for combinational therapy could be an effective strategy.

Methods

Herein, we used the electrostatic assembly method to develop smart therapeutics with targeting ligand of hyaluronan (HA) for tumor photothermal treatment. Furthermore, we calculate the photothermal property and photothermal conversion efficiency under prominent irradiation. Then, we co-encapsulated the immuno molecues for to trigger immunne responses against the tumors. In vivo analysis of photoimmunotherapy efficacy of targeted therapy in mice models was done.

Results

Encouragingly, therapeutics have selective receptor-targeted specific endocytic uptake of TNBC and incinerates the tumor under irridiation releasing tumor-associated antigens. Furthermore, co-encapsulated imiquimod (R837) immunoadjuvant molecules trigger strong immune response against post-phototherapy of tumor. Therefore, nanotherapeutics based photoimmunotherapy is an effective combined treatment for TNBC to protect the mice from cancer relapse and metastasis.

Conclusions

We conclude that results of smart therapeutics platform could serve as a new photoimmunotherapy modality for future clinical use. Combined cancer immunotherapy has the greatest potential for the treatment of cancer and prevention of future relapse by the activation of the immune system to recognize and kill tumor cells.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

77P - Dual targeting oxidative phosphorylation and glycolysis in triple-negative breast cancers: En route to effective inhibition of tumour metabolism (ID 470)

Presentation Number
77P
Lecture Time
09:00 - 09:00
Speakers
  • Alexander M. Scherbakov (Moscow, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Triple-negative breast cancer is a highly aggressive type of breast tumors characterized by the lack of targets for hormone and anti-HER2 therapy. Inhibition of tumor metabolism is one of the promising approaches in the treatment of triple-negative breast cancer. As shown by previous studies, single treatments with oxidative phosphorylation (OxPhos) or glycolysis inhibitors were ineffective. The work aimed to develop novel oligomycin derivatives (OxPhos inhibitors) and evaluate their activity in combination with glycolysis inhibitors, 2-deoxyglucose (2DOG) and 3-bromopyruvate (3BP).

Methods

MCF-7 and MDA-MB-231 breast cancer cell lines and MCF-10A human mammary epithelial cells were obtained from the ATCC collection. Antiproliferative activity was measured by the MTT test. Immunoblotting was used for the assessment of signaling proteins.

Results

New derivatives of oligomycin A have been obtained using Diels-Alder reactions. Using a screening, a lead derivative of oligomycin A, LCTA-3056, was selected, which is characterized by high selectivity for triple-negative breast cancer cells. Low toxicity of LCTA-3056 was revealed for MCF-10A human mammary epithelial cells. The high activity of combinations of LCTA-3056 with metabolic inhibitors, 3BP and 2DOG, against MDA-MB-231 triple-negative cancer cells was shown. Moreover, the combination of LCTA-3056 with 3BP modulated AMPK/mTOR/S6K pathway and effectively reversed the aggressive EMT phenotype of triple-negative breast cancer cells.

Conclusions

Combinatorial approach with oligomycin A derivatives may hold promise in the development of therapies against triple-negative breast cancers, including those with acquired resistance to standard chemotherapy. The research was supported by the Russian Foundation for Basic Research (# 18-015-00422, experiments with 2DOG) and Russian Science Foundation (#19-15-00245, experiments with MCF-7 cells).

Legal entity responsible for the study

The authors.

Funding

The Russian Foundation for Basic Research (# 18-015-00422, experiments with 2DOG) and Russian Science Foundation (#19-15-00245, experiments with MCF-7 cells).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

78P - Novel allogeneic cell immunotherapy for advanced cancers (ID 518)

Presentation Number
78P
Lecture Time
09:00 - 09:00
Speakers
  • Ratnavelu Kananathan (Nilai, Negeri Sembilan, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immune checkpoint inhibitor (ICI) and CAR-T cell immunotherapies have provided new treatment options for many patients with metastatic disease and hematological malignancy, respectively, inducing durable responses in some cases. CAR-T is not indicated for solid tumors and ICI responsiveness requires high tumor mutational load, CD8+ T cell infiltration and positive IFN-γ status, defining an inflamed phenotype (“hot tumors”). However, the majority of metastatic tumors present as non-inflamed (“cold tumors”), thus limiting the applicability of ICI to a minority subset of patients with highly immunogenic tumors. Immunological treatment of cold tumors is a great challenge as no pre-existing adaptive immune response has been established or maintained.

Methods

AlloStim®, was used on compassionate grounds AlloStim® is currently being evaluated in a phase IIB clinical trial in USA in MSI-S, chemotherapy-refractory, metastatic colorectal cancer patients, an indication known to present with “cold” lesions and to be non-responsive to ICI. AlloStim® is a living, non-genetically manipulated, allogeneic Th1-like cell therapy derived from precursor cells purified, expanded and differentiated from blood of normal donors. The AlloStim® mechanism of action is purported to convert “cold” tumors to “hot” tumors and naturally down-regulate checkpoint molecules in the tumor microenvironment. Single dose vials of formulated AlloStim® cells were delivered to our center in liquid nitrogen dry shippers. Administered either intradermally (ID) or intravenously (IV). The protocol included 3 weekly intradermal (ID) injections followed a week later by an intravenous (IV) infusion. This 4-week cycle was repeated 3 times. Upon approval of our institutional review board and obtaining informed consent.

Results

7 patients were acured 3 advanced/metastatic hepatocellular carcinoma, 2 breast cancer, 1 gall bladder and 1 Nasopharyngeal cancer. Due to the advanced status and poor ECOG status, only 3 completed the treatment schedule. 2 were still stable and alive at 1-year follow-up without receiving any other systemic therapy.

Conclusions

Simple to administer, minimal side-effects and appears to have activity in refractory metastatic disease. Further controlled clinical trials is warranted.

Legal entity responsible for the study

Kananathan.

Funding

Has not received any funding.

Disclosure

M. Har Noy: Leadership role, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Mirror Biologics Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Gastrointestinal tumours, colorectal (ID 1145)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

86P - The impact of sarcopenia on chemotherapy toxicity and survival rate among colorectal cancer patients who underwent chemotherapy: A systematic review and meta-analysis (ID 227)

Presentation Number
86P
Lecture Time
09:00 - 09:00
Speakers
  • Timotius I. Hariyanto (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Colorectal cancer (CRC) is the third most commonly diagnosed cancer globally and the second cancer in terms of mortality. The prevalence of sarcopenia in patients with CRC ranges between 12%-60%. It has been described that there is an association between sarcopenia and numerous poor short-term CRC outcomes like increased perioperative mortality, postoperative sepsis, prolonged length of stay, and physical disability. In this study, we review the evidence regarding the impact of sarcopenia and low muscle mass on chemotherapy toxicity and survival among colorectal patients who underwent chemotherapy.

Methods

A systematic review was performed according to PRISMA guidelines. A literature search was conducted by two independent reviewers on all studies that included sarcopenia in colorectal cancer patients who underwent chemotherapy using PubMed, PubMed central, and Google Scholar databases. Study included elderly population was excluded. Outcome of interest included chemotherapy toxicity and overall survival. Data synthesis and statistical analysis were carried out using Review Manager software.

Results

A total of 2206 patients from 14 studies were included in our meta-analysis. In our overall analysis of chemotherapy toxicity, we indicated that CRC patients with sarcopenia would have higher incidence of chemotherapy toxicity (OR = 1.91, 95% CI = 1.37 – 2.67, P < 0.001) including grade 3/4 neutropenia, peripheral neuropathy, nausea and vomiting, also diarrhea. Regarding survival outcomes, our results showed that sarcopenia associated with a decreased overall survival (HR = 1.64, 95% CI 1.36 – 1.98, P < 0.001). These effects of sarcopenia and low muscle mass on chemotherapy toxicity and overall survival were observed among various chemotherapy regimens and across disease stages.

Conclusions

Sarcopenia and low muscle mass can give negative impact on chemotherapy toxicities and survival outcomes for colorectal cancer patients who underwent chemotherapy. Prospective studies with a uniform definition of sarcopenia are still needed to update our findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

87P - Predictive risk factors and online nomograms for colon cancer with synchronous liver metastasis (ID 187)

Presentation Number
87P
Lecture Time
09:00 - 09:00
Speakers
  • Yajuan Zhu (Chengdu, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Liver metastases were observed in more than 25% of colon cancer patients when initially diagnosed. We aim to perform a retrospective analysis to investigate the pathological characteristics and treatment experience of synchronous liver metastasis (CLM) using data from the Population-based Surveillance, Epidemiology, and End Results (SEER) database. Furthermore, we intend to identify potential prognostic factors and build origin predictive models for evaluating 3-year and 5-year cancer-specific survival (CSS) and overall survival (OS) of CLM.

Methods

CLM patients were collected from SEER database between 2010 and 2015. Univariate and multivariate cox regression analyses were conducted to identify the potential predictors of patient’s survival outcomes. The selected variables were integrated to create predictive nomograms via R tools. Furthermore, the concordance index Harrell’s C statistic (C-index) was calculated to describe the discrimination of nomograms. Calibration (1000 bootstrap resamples) curves were plotted to compare predictions of the nomogram and observed outcomes. Subsequently, Decision Curve Analysis (DCA) and clinical impact curves were performed to evaluate the clinical effects of nomograms.

Results

Total 11,812 CLM patients were included after eliminating those with missing information. Tumor primary site, tumor size, histological grade, T /N stage, surgery of other regions, bone/lung metastasis, CEA level, tumor deposits, regional positive nodes, and chemotherapy were used to construct the predictive models of CSS and OS of CLM. Final nomograms indicated relatively good discrimination (C-index = 0.74 for OS and C-index = 0.73 for CSS). The calibration curves of CSS and OS suggested a good agreement. In addition, DCAs and clinical impact curves reflected favorable potential clinical effects. Online webserver of our nomograms was established for convenient utilization (https://predictivetools.shinyapps.io/CSSDynNomapp/;https://predictivetools.shinyapps.io/OS-DynNomapp/).

Conclusions

The nomograms were built on the webserver and validated to effectively and timely predict the CSS and OS of colon cancer patients with synchronous liver metastasis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

88P - Research of radiomics based on indeterminate lung nodules predicting prognosis of LARC patients (ID 327)

Presentation Number
88P
Lecture Time
09:00 - 09:00
Speakers
  • Zhang Zhiyuan (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

With lung remains the second common site of colon-rectal cancer metastasis, it is still a challenge for early detection and finding. Therefore, we evaluate the CT-based radiomics of indeterminate lung nodules, predicting lung metastasis and prognosis in locally advanced rectal cancer patients.

Methods

A retrospective review for lung metastatic patients with colon-rectal cancer (CRC) and chest CT images were conducted. Radiomic prediction model of lung metastasis was trained by 114 patients with pathologically verified lung metastasis and 122 patients with benign lung nodules. We investigate the value of radiomics for identifying lung metastasis in 174 locally advanced rectal cancer(LARC) patients with follow-up information. Then, we conducted a Cox model and Kaplan-Meier curve analysis based on radiomics risk scores, and compare them to a clinical-pathological model for prognostic prediction. We use LASSO and linear regression to generated the radiomics model. C-index was used to assess model performance.

Results

For lung metastatic nodule identification in CRC patient, the C-index was 0.794(95%CI 0.784 -0.803) in the training set and 0.752(95%CI 0.728-0.776) in the validation set. In LARC patients, the C-index for lung metastatic identification was 0.771(95%CI 0.763-0.780). For prognostic prediction in LARC patients, ypTNM stage had a great influence on prognosis(Log-rank test P=0.003), and the C-index was 0.695 (95%CI 0.638-0.752). The C-index for nodules was 0.663(95%CI 0.575-0.751) with HR=1.148 (95% 1.050-1.256, P=0.003), and P<0.001 for Log-rank test. The combination of the ypTNM stage and nodule radiomics information has the C-index of 0.757 (95%CI 0.692-0.822), with P<0.001 for Log-rank test, which increase the performance of clinical prognostic prediction(P= 0.044).

Conclusions

Radiomics for nodules can determine lung metastasis in LARC patients. Lung nodules radiomics can provide information for prognostic analysis. The combination of lung nodules radiomics and ypTNM information increases the performance of prognostic prediction in LARC patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

89P - Biomarker analysis of regorafenib dose escalation study (RECC study): A phase II multicenter clinical trial in Japan (ID 491)

Presentation Number
89P
Lecture Time
09:00 - 09:00
Speakers
  • Masanobu Enomoto (Shinjuku-ku, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

RAS status can impact on efficacy of chemotherapy for patients with metastatic tumor. However, we reported that RAS mutated clone can emerge in patients with RAS wild tumor, which suggest that the genotype of the tissue obtained at the time of diagnosis might not accurately represent, who are treated with EGFR blockade. In this study, we evaluated whether RAS mutation in tissue and/or in circulating tumor DNA (ctDNA) impact on efficacy of regorafenib. This is the biomarker analysis of RECC study, a phase II multicenter clinical trial in Japan, that confirmed the safety and effectiveness of dose escalation therapy of regorafenib in metastatic colorectal cancer (mCRC).

Methods

We conducted dose-escalation study as a single-arm, prospective, non-randomized, multi-centered open label phase II trial in Japan (RECC study). We set a starting dose of 80 mg/day during the first seven days, then will be increased up to 120 or 160 mg/day weekly. Before first administration of regorafenib, we extracted ctDNA and examined RAS mutation in ctDNA using droplet digital PCR (ddPCR).

Results

Fifty-eight patients with mCRC were registered in this study, and blood samples were available in 45 patients. In all obtained samples, ctDNA were successfully extracted from plasma and the quality and quantity of ctDNA were sufficient for genetic analysis. RAS mutation was detected in tumor tissue of 29 patients (64%) and in ctDNA of 21 patients (47%). In ctDNA, RAS mutation was detected in 21 of the 29 patients (72%) with RAS mutated tumor, and 6 of 16 patients with RAS wild tumor. Five of the 6 patients with RAS wild tumor were treated with EGFR blockade in previous treatment. RAS status both in tumor tissue and ctDNA had no impact on progression free survival and overall survival.

Conclusions

It was reported that RAS mutation has negative impact on efficacy of FTD/TPI. However, RAS mutation showed no impact on the efficacy of regorafenib. EGFR blockade have a potential to emerge RAS mutated clone. Thus, RAS status should be reconfirmed at the last minute before starting late line chemotherapy using liquid biopsy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

90P - The role of miR-133a-3p/SP1/IGF1R axis in the progression of colorectal cancer (ID 519)

Presentation Number
90P
Lecture Time
09:00 - 09:00
Speakers
  • Hui Li (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. MicroRNA has been reported playing an important role in a variety of cancers including colorectal cancer.

Methods

CRC tissues as well as CRC cell lineswere used to evalute the expression and function of miR-133a-3p, SP1 and IGF1R. The relationship between miR-133a-3p and clinical-pathological charateristics of CRC patients were analyzed. The interaction among miR-133a-3p/SP1/IGF1R was assessed using Dual Luciferase reporter.

Results

MiR-133a-3p has been found down-regulated in CRC tissues compared with the adjacent normal tissues. The expression of miR-133a-3p was significantly associated with histological differentiation (P=0.01) and TNM stage (P=0.006) respectively. CRC patients with low miR-133a-3p expression had a significantly shorter survival time than those patients with high miR-133a-3p expression (P=0.04). Gain-of-function assays showed that miR-133a-3p inhibited cellular proliferation and colony formation, but had no effect on migration and invasion of CRC cells. Furthermore, expression of SP1 and IGF1R was reduced by elevating miR-133a-3p expression in CRC cells. Luciferase assay further confirmed that SP1 but not IGF1R was the target gene of miR-133-3p and SP1 could bind to the promoter region of IGF1R gene.

Conclusions

In summary, our findings first demonstrate that miR-133a-3p acts as a tumor suppressor by targeting SP1 and miR-133a-3p/SP1/IGF1R signaling pathway is involved in CRC progression. MiR-133a-3p may be a novel molecular therapeutic target for CRC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

91P - Prognostic biomarker of clinical outcome in locally advanced rectal cancer in Chinese patients (ID 576)

Presentation Number
91P
Lecture Time
09:00 - 09:00
Speakers
  • Sandy S. Ho (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Neoadjuvant chemoradiotherapy (NCRT) is one of the standard treatments for locally advanced rectal cancer (LARC), where pathological complete response (ypCR) has been traditionally used as a surrogate survival endpoint. A relatively new biomarker known as the Neoadjuvant Rectal (NAR) score has been consistently shown to correlate with survival in clinical studies. NAR score is a composite endpoint combining clinical and pathological staging information obtained before and after NCRT which warrants validation in local population. The main objective of this study is to investigate the factors that may influence the achievement of ypCR, such as age, sex, tumour stage and location, presence of threatened CRM and extramural vascular invasion (EMVI) as well as tumour down-staging. Other objectives are to validate the prognostic significance of NAR score and to investigate any factors that are associated with a lower score.

Methods

The data of patients with LARC who received NCRT at the Prince of Wales Hospital between August 2006 to October 2018 were retrospectively analyzed. Chi-square or Fisher’s Exact Test was used to determine any correlation between categorical variables and logistic regression for continuous variables. Cox regression was used to determine any interactions between covariates and Kaplan-Meier method for survival analysis.

Results

Of the 193 patients who had optimal response to NCRT and surgery, the mean age was 62 and the male-to-female ratio was 2.94: 1. Tumour down-staging was the only independent prognostic factor which predicted ypCR (p<0.0001). NAR score was associated with overall survival (OS) (hazard ratio, HR=1.042, 95% confidence interval, CI: 1.021-1.064, p<0.0001), disease-free survival (DFS) (HR=1.042, 95% CI: 1.022-1.062, p<0.0001), locoregional recurrence-free survival (LRFS) (HR=1.070, 95% CI:1.039-1.102, p<0.0001) and distant recurrence-free survival (DRFS) (HR=1.034, 95%CI: 1.012-1.056, p=0.002). Patients who had ypCR to NCRT was associated with a lower NAR score (p<0.0001), but ypCR was not associated with survival.

Conclusions

NAR score (but not ypCR) is an independent prognostic marker of survival and disease recurrence in a cohort of Chinese patients who underwent NCRT for LARC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

92P - Development and validation of risk and prognostic nomograms for bone metastases in advanced colorectal cancer patients (ID 665)

Presentation Number
92P
Lecture Time
09:00 - 09:00
Speakers
  • Nan Wang (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Bone metastases (BM) from colorectal cancer (CRC) are often accompanied by extraosseous metastases and have a dismal prognosis. The present study aims to find out the risk factors for BM in metastatic CRC (mCRC) and the prognostic factors for CRC patients with BM.

Methods

The study was based on a training cohort of 214 mCRC patients (of which 101 patients with BM) from our center, and a validation cohort of 511 mCRC patients from another institution (of which 173 patients with BM). The risk and prognostic nomogram for BM were identified using univariate and multivariate analyses. The goodness of fit, discrimination and calibration performance of the nomograms were assessed by R2, concordance statistics (C-statistics) and the calibration curve. The results were internally validated using bootstrap resampling in the training cohort and externally validated in the validation cohort.

Results

The novel BM risk nomogram comprised of seven variables (degree of tumor differentiation, N_stage, serum ALP, LDH, CEA, liver metastasis and lung metastasis). It showed good performance with an R2 of 0.447 and a C-statistics of 0.846 (95% CI, 0.793 to 0.898) in the training cohort, and an R2 of 0.325 and a C-statistics of 0.792 (95% CI, 0.750 to 0.834) in the validation cohort. The optimal cutoff value to identify individuals at low or high risk was 56% probability with the sensitivity of 71.3% and specificity of 89.4%. The prognostic nomogram included five factors (tumor differentiation, No. of extra-BM organs, No. of BM lesions, ALP and LDH) with an R2 of 0.284 and a C-statistics of 0.723 (95% CI, 0.657 to 0.789) in the training set. This nomogram was externally validated in the validation cohort with an R2 of 0.182 and a C-statistics of 0.682 (95% CI, 0.638 to 0.726).

Conclusions

The developed and validated risk nomogram and prognostic nomogram show good performance on predicting the occurrence of BM in mCRC and prognosis in CRC patients suffered from BM. The risk nomogram can be used as a cost-effective preliminary screening tool prior to bone scan.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

93P - Assessment of nutritional status of colorectal cancer patients in a tertiary government hospital (ID 787)

Presentation Number
93P
Lecture Time
09:00 - 09:00
Speakers
  • Rogelio N. Velasco (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Malnutrition, a problem often missed among patients with colorectal cancer, can result in decreased survival. However, its prevalence has not yet been evaluated in our institution. This study aimed to determine the nutritional status among patients with colorectal cancer at the Philippine General Hospital and identify predictors for malnutrition.

Methods

A cross-sectional study was conducted among all patients with colorectal cancer seen at the Philippine General Hospital Cancer Institute between December 2019 to February 2020. Anthropometric measurements were taken and nutritional status was evaluated using the Subjective Global Assessment tool. Descriptive statistics, ANOVA and logistic regression were employed to analyze the data.

Results

A total of 292 participants were included in the study with a high prevalence of cachexia (25.34%), sarcopenia (31.16%), and malnutrition (76.37%). Notably, only 17% of patients were referred by oncologists to the dietary service. The presence of liver metastasis and multiple sites of metastases were associated with increasing degree of malnutrition across SGA B and C (p = 0.05). Additionally, more patients with lung and peritoneal metastases were classified as malnourished (p = 0.05). Patients who did not receive chemotherapy, radiation, or surgery were more likely to be malnourished compared to those who previously received or were currently receiving treatment (chemotherapy: p < 0.01; radiation: p = 0.04; surgery: p < 0.01). Furthermore, patients with stage III disease had a higher odds for malnutrition (OR: 6.22, p < 0.01) compared to those with stage I and II disease, while patients who received or were currently receiving chemotherapy were less likely to have malnutrition than those who did not (OR: 0.35, p < 0.01).

Conclusions

Due to the high prevalence of malnutrition among patients with colorectal cancer, routine nutritional evaluation is important. Moreover, the high prevalence of cachexia and sarcopenia warrants early and adequate nutritional intervention. Thus, a hospital-wide program focusing on early nutritional assessment is recommended for implementation.

Legal entity responsible for the study

The authors.

Funding

Philippine General Hospital.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

94P - Prognostic influence of mean platelet volume on stage III rectal cancer patients: A tertiary cancer center study (ID 390)

Presentation Number
94P
Lecture Time
09:00 - 09:00
Speakers
  • Pavan K. Jonnada (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Mean platelet volume (MPV) is a marker of inflammation that indicates the average size of platelets, platelet production rate and stimulation. The role of Pre-operative levels of MPV and its prognostic effect on disease free survival (DFS) and overall survival (OS) are poorly understood. This study was intended to analyze the effect of pre-operative levels of MPV on DFS and OS of stage III rectal cancer patients.

Methods

This is a retrospective study of 149 stage III rectal cancer patients who underwent surgery in our institution between 2011 and 2015. Association between pre-operative levels of MPV and clinicopathological variables were analysed. DFS and OS for 5 years were analysed, and survival analysis was done using Kaplan-Meier curve. MPV of 9.35 femto litres (fl) was chosen based on the ROC curve. The Area under curve was 0.889. Differences between survival curves were analysed for statistical significance using log-rank test.

Results

In our study, mean 5-year OS were 91.1 and 50.36 months, for patients with MPV < 9.35 and MPV >9.35 respectively (P 0.0001). The mean DFS of MPV < 9.35 and MPV > 9.35 were 89.32 and 43.54 months respectively (P 0.0001). Univariate analysis for OS and DFS showed significance for MPV, Nodal status, Circumferential resection margin, stage and lymph node ratio. Multivariate analysis showed significance for MPV [HR 2.379 (95% CI 1.733-3.264) P .0001 for MPV>9.35] and CRM [HR 0.392 (95% CI 0.191-0.804) P 0.01) for CRM negative] for OS and DFS. Multivariate Analysis for OS & DFS

Variable OS DFS
P value Hazard Ratio 95% CI P value Hazard Ratio 95% CI
Lower Upper Lower Upper
N Stage
N1a .782 .785 .140 4.390 .824 .833 .167 4.146
N1b .119 .322 .077 1.340 .159 .389 .104 1.448
N2a .554 .715 .235 2.175 .680 .810 .297 2.209
N2b Reference Reference
CRM
Negative .011 .392 .191 .804 .012 .412 .207 .821
Positive Reference Reference
Stage
IIIA .568 .692 .196 2.447 .203 .465 .143 1.510
IIIB .474 .727 .303 1.743 .203 .607 .281 1.310
IIIC Reference Reference
MPV
>9.35 .0001 2.379 1.733 3.264 .0001 2.370 1.791 3.136
<9.35 Reference Reference
LNR ratio
>0.2 .220 3.269 .492 21.738 .059 5.756 .938 35.327
<0.2 Reference Reference
.

Conclusions

Pre-operative MPV measured one week before surgery is a convenient and inexpensive marker which has been proved to be a prognostic marker for OS and DFS in stage III rectal cancer patients.

Legal entity responsible for the study

Kidwai Memorial Institute of Oncology, Bangalore, India.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

95P - Prognosis of Japanese patients with detailed RAS/BRAF mutant colorectal cancer (ID 427)

Presentation Number
95P
Lecture Time
09:00 - 09:00
Speakers
  • Tatsuki Ikoma (Kobe, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

RAS mutations are the most prominent oncogenic driver mutations in cancers, including colorectal cancer. Patients with metastatic colorectal cancer (mCRC) with mutant RAS are ineligible for anti-epidermal growth factor receptor (EGFR) therapy, as RAS mutations activate downstream pathways independently of EGFR and induce primary resistance. In particular, mutations in the amino acid at position 12 in the KRAS protein are common, and the KRAS p.G12C mutation occurs in ∼3% of CRC cases and is often associated with poor prognosis. Nevertheless, no agent directly targeting mutant RAS has been clinically approved. The CodeBreak 100 trial revealed that a novel KRASG12C inhibitor, AMG510, has an attractive anti-tumor effect against KRASG12C-mutant solid tumors, including mCRC. However, there are no data about the clinical and prognostic features in Japanese patients with detailed RAS/BRAF V600E-mutant mCRC including KRASG12C. The aim of this multicenter retrospective study was to investigate the clinical and prognostic features in Japanese patients with detailed RAS/BRAF V600E-mutant mCRC.

Methods

Between August 2018 and July 2019, chemotherapy-naïve patients with mCRC from whom samples were collected and investigated for all RAS/BRAFV600E statuses were included in this study. The RAS/BRAFV600E status was determined using the MEBGEN RASKET-B kit, PCR-rSSO method.

Results

In total, 152 patients with mCRC (median age, 71 years; male, 71%; left-sided primary, 67.1%) were enrolled from three tertiary cancer centers. Of the patients, RAS/BRAF mutations were detected in 54.6% (KRAS codon 12, 27.0%; KRAS codon 13, 11.8%; minor RAS, 9.2%; BRAFV600E, 6.6%). BRAFV600E-mutant tumors were predominantly located on the right side (77.8%, p=0.005), and minor RAS-mutant tumors were located predominantly on the left side (92.9%, p=0.037). Minor RAS-mutant tumors were associated with significantly shorter survival times than those associated with RAS wild-type {hazard ratio (HR)=2.65 [95% confidence interval (CI), 0.99 to 7.07], p=0.043} and major RAS-mutant tumors (HR=5.15 [95% CI, 1.56 to 16.98], p=0.003).

Conclusions

This multicenter study revealed the clinical and prognostic features in Japanese patients with detailed RAS/BRAFV600E-mutant mCRC.

Legal entity responsible for the study

Hironaga Satake.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

96P - Early-onset colorectal cancer prognosis, conflict resolution, review of literature and meta-analysis (ID 817)

Presentation Number
96P
Lecture Time
09:00 - 09:00
Speakers
  • Ereny S. Poles (Assiut, Egypt)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Early-onset colorectal cancer (EOCRC) is defined as colorectal cancer diagnosed in individuals younger than 50 years old. There is a concept that EOCRC is associated with a worse survival, while the data on literature is conflicting. Evaluation of the available data is highly needed to reach an evidence-based conclusion.

Methods

A systematic literature search was performed using Scopus (2015-2020), CENTRAL PubMed (2015-2020) for studies assessed prognosis of EOCRC in comparison with LOCRC using the relative 5-year survival (OS) as a surrogate for prognosis. Extracted information included: study identification, number of EOCRC and LOCRC patients, AJCC stage, and overall 5-year survival. Keywords and Mesh words used: prognosis, outcome, survival, young, early-onset, age of onset, colorectal cancer, rectal cancer, colon cancer. Statistical analysis was done using MedCalc Statistical Software for the meta-analysis.

Results

Meta-analysis for a total of 428554 LOCRC and 670030 EOCRC patients of the included 9 studies showed no statistically significant difference in male ( P= 0.19 ) or female ( P= 0.20 ) as regards the incidence EOCRC when compared to LOCRC. Younger adults were1.2 more likely to present with left-sided and rectal cancer ( OR;1.20, 95% CI, 0.18 to 7.86, P= 0.84 ) than older patients, while the right colon cancer was less presented by 79% in EOCRC patients (OR; 0.79, 95%CI, 0.05 to 11.13, P= 0.86). Stage I disease was statistically significant less diagnosed in EOROC than LOCRC patients ( P< 0.001, 95%CI, 0.31 to 0.70 ), while there were no statistically significant differences for stages II, III, and IV, ( P= 0.27, 95%CI, 0.03 to 2.58), ( P= 0.84, 95%CI, 0.03 to 4.57) and ( P= 0.70, 95%CI, 0.10 to 4.62 ) respectively. There was no difference in the 5 year OS between EOCRC and LOCRC patients ( P= 0.62, 95%CI, -0.004 to 0.002). Subgroup analysis based on the stage showed a better survival in EOCRC patients in all stage groups; ( P= 0.03, 95%CI,1.34 to 21.19) for stage I, (P, 0.001, 95%CI, 2.38 to 3.64) for stage II, (P< 0.001, 95%CI, 2.20 to 4.80) for stage III, and (P= 0.009, 95%CI, 1.62 to 28.79) for stage IV.

Conclusions

EOCRC patients had a similar 5-year OS when compared to LOCRC while had a better 5-year OS when corrected for the disease stage.

Legal entity responsible for the study

The authors.

Funding

Quality Control Unit, Faculty of Medicine, Assiut University.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

97P - A population-based study to assess the associations of rural residence and low socioeconomic status (SES) with cardiovascular disease (CVD) in patients with colorectal cancer (CRC) (ID 252)

Presentation Number
97P
Lecture Time
09:00 - 09:00
Speakers
  • Atul Batra (New Delhi, Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients with CRC are predisposed to CVD due to shared risk factors and sequalae of cancer treatments. We aimed to assess if rural residence and low SES modify the risk of developing new-onset CVD in patients with CRC.

Methods

Patients diagnosed with stage I-III CRC without any baseline CVD in a large Canadian province from 2004 to 2017 were identified using the population-based registry. Postal codes were linked with Census data to determine rural residence as well as SES. Low income and low education were defined as <46,000 CAD/annum and a neighborhood population in which <80% attended high school. The presence of myocardial infarction, heart failure, arrythmia or cerebrovascular accident constituted as CVD.

Results

We identified 12,170 eligible patients. The median age was 65 years and 43.7% were women. Stage I, II and III CRC were diagnosed in 30.2%, 31.4% and 38.5% patients. One-fourth of patients resided rurally, while 78.8% and 59.5% belonged to low income and low education neighborhoods. At a median follow-up of 62.2 months, 4,163 (34.2%) developed new-onset CVD, which was more common in patients from rural communities (36.8% vs 33.3%, P<.001), low income (35.7% vs 28.8%, P<.001) and low education (36.0% vs 31.6%, P<.001) neighborhoods. After adjusting for age, sex and treatment, low income (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.10-1.37; P<.001) and low education (OR, 1.10; 95% CI, 1.01-1.20; P=.044) were associated with a higher likelihood of developing CVD, while rural residence was not. In a Cox regression model adjusting for measured confounders, low income (hazard ratio, 1.14; 95% CI, 1.03-1.25; P=.010) but not low education and rural residence predicted for worse overall.

Conclusions

In this large population-based study, patients from low SES neighborhoods were at an increased risk of developing new-onset CVD. However, the effect on survival was attenuated, likely reflecting access to universal healthcare in Canada. SES disparities in physical activity, diet, and other lifestyle modification strategies may explain the different risk profiles for CVD and should be the focus of public health efforts.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

98P - Operational challenges of an Asian Pacific (APAC) academic oncology clinical trial (ID 928)

Presentation Number
98P
Lecture Time
09:00 - 09:00
Speakers
  • Daphne Day (Clayton, Ontario, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Multinational academic trials can pose complex organisational issues. We describe our experience running the phase III ASCOLT trial (NCT00565708), studying the impact of aspirin in resected high-risk colorectal cancer. This is the first large academic adjuvant trial fully conducted in the APAC region.

Methods

ASCOLT is coordinated by the National Cancer Centre Singapore and funded largely by academic grants. The trial opened in 2008 and is nearing full accrual (1480 of 1587) at 58 sites in 12 countries/regions, including 5 middle income countries. Trial conduct logistics were analysed to identify barriers and enablers.

Results

Diverse regulatory requirements necessitated >100 contracts and 49 ethics board reviews, leading to start up times of ∼6 months per site. Consent forms were translated into 13 languages. The enrolment target and period were revised in 2017, and site numbers expanded due to lower than projected accrual and event rates. Other challenges include communication and logistical barriers, patient attrition, recruitment holds due to changes in local laws and limited funding for patient visits, affecting countries where healthcare is not publicly funded. Solutions included engaging local cooperative groups (e.g. the Australasian GastroIntestinal Trials Group in Australia and New Zealand) and 6 contract research organisations to manage sites, developing processes sensitive to local needs, transition to electronic data management, and a centralised drug dispensing system. Measures to overcome disparate experience across sites and to quality control include regular contact with the central team to troubleshoot (e.g. >200 data queries are raised a month) and central and on-site monitoring. 16 sites were closed due to resource or recruitment issues. In response to the COVID-19 pandemic, strategies such as telehealth consults, direct postage of drugs to patients, consent form amendments, and rationalised recruitment and biospecimen collection were swiftly applied.

Conclusions

While ASCOLT highlights the feasibility and value of APAC academic collaborative trials, our challenges reflect the complexities in a region of cultural, linguistic, economic and regulatory diversity. An APAC academic trials consortium is suggested.

Clinical trial identification

NCT00565708.

Legal entity responsible for the study

National Cancer Centre Singapore.

Funding

National Cancer Centre Singapore.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

99P - Development of a qRT-PCR-based diagnostic test to identify colorectal cancer patients with recurrent R-Spondin gene fusions (ID 245)

Presentation Number
99P
Lecture Time
09:00 - 09:00
Speakers
  • Veronica Diermayr (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In colorectal cancers (CRC) 4 different recurrent gene fusions involving R-Spondin (RSPO)2/3 and different exons of PTPRK or EIF3E are found with around 4% incidence. These fusions (Fusion A-D) occur exclusively in a sub-population of CRC with high unmet medical need that is microsatellite-stable (MSS) and mutant for KRAS, NRAS or BRAF but wild-type (WT) for APC. RSPO-fusions are known driver mutations, increasing Wnt signalling and sensitizing for treatment with upstream Wnt pathway inhibitors. Detection of the fusions is possible using Archer FusionPlex technology, but with low sensitivity. A multiplex reverse transcription, real-time PCR-based test, specific for the detection of recurrent RSPO fusions, was developed as a Clinical Trial Assay (CTA).

Methods

The CTA uses RNA extracted from FFPE or frozen tumor tissue in a qRT-PCR, simultaneously detecting the RSPO fusion, the WT fusion partner(s), and an internal control. The assays span exon-exon junctions to increase selectivity and amplify fragments of 80-140 bp in length to allow for detection in RNA extracted from FFPE tissue. A ΔCt is calculated by subtracting the Ct of the WT reaction (PTPRK or EIF3E) from the RSPO fusion Ct. Values below or equal to the set cut-off permit qualitative calling of samples positive for the fusions.

Results

180 fresh frozen and 118 FFPE samples from CRC patients were used in the analytical validation for the 4 CTAs. All assays show high precision (100%) at the limit of detection (LoD) and high specificity in terms of residual EtOH (≤4%) or EDTA (<5 mM). Sensitivity was high with the LoD for Fusions A-D between 1.46-5.10% for frozen tissue and 2.82%-21.6% for FFPE, respectively. The assays also showed high accuracy and 100% concordance with Sanger sequencing for fusion positive samples (with a ΔCt cut-off of ≤13-15 and ≤5-7.5 for frozen and FFPE tissue, respectively).

Conclusions

The RSPO Fusion CTA is a quick and cost-effective test with high sensitivity (RNA input of 5 or 25 ng for frozen and FFPE tissue respectively). This CTA is currently used to pre-screen & select patients for the phase IB trial with the porcupine inhibitor ETC-1922159 (NCT02521844) ongoing in Singapore and USA.

Clinical trial identification

NCT02521844.

Legal entity responsible for the study

Experimental Drug Development Centre, A*STAR.

Funding

BMRC, NRF and NMRC Singapore.

Disclosure

V. Diermayr: Research grant/Funding (institution), Full/Part-time employment: A*STAR. S. Sarma, K.F.Y. Lee, B.H. Gan: Full/Part-time employment: A*STAR. M. Inoue: Licensing/Royalties, Full/Part-time employment: A*STAR. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

100P - Individualized treatment of advanced digestive system tumour guided by PDTX mouse model: A multicenter trial (ID 499)

Presentation Number
100P
Lecture Time
09:00 - 09:00
Speakers
  • Yuan Cheng (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To explore the clinical feasibility of the patient-derived tumor xenograft (PDTX or PDX) mouse model in guiding the individualized precise treatment of advanced digestive system tumors through a multicenter clinical study.

Methods

14 centers participated the trial in China. Fresh tumor tissues were obtained by surgery and biopsy, then engrafted subcutaneously into immune deficient mice. When the tumor volume grew to 60 mm3, the modeling was successful. The consistency of the original tissue (PA) and the engrafted tissue (P0) was analyzed by pathological comparison. The tumorigenesis time model was recorded. After successful modeling, medication was administered in groups according to the recommended regimen for 21 days. The tumor growth inhibition rate (TGI) was recorded and evaluated as positive if TGI > 60%. According to RECIST 1.1, DCR (SD, PR, CR) was evaluated as positive in clinical synchronous treatment. The two results were compared to evaluate the accuracy of guiding clinical medication.

Results

A total of 33 patients with different advanced digestive system tumors were included, including 2 cases of esophageal cancer, 10 cases of colorectal cancer, 10 cases of pancreatic cancer, 5 cases of gastric cancer, 3 cases of liver cancer, 2 cases of duodenal adenocarcinoma and 1 case of gallbladder cancer. The successful rate of tumor xenograft modeling was 75.8% (25/33), including 78.3% (18/23) in small samples and 70% (7/10) in surgical samples. Pathological results showed that the consistency of P0 and PA was 100% in 25 cases. The average tumorigenesis time of PDTX model was 42 days. Pharmacodynamic tests were completed in 17 cases, including 28 kinds of drugs and 49 regimens. The clinical efficacy of 10 regimens in 9 patients were evaluated as PR in 2 cases, SD in 6 cases and PD in 2 cases. The results of pharmacodynamic test were consistent with clinical synchronous efficacy.

Conclusions

PDTX mouse model has high successful modeling rate with the biological and pathological characteristics of primary tumor, and the results of pharmacodynamic test are highly consistent with the clinical efficacy. It can be used as a individualized diagnosis and treatment technique of advanced gastrointestinal tumors.

Legal entity responsible for the study

The authors.

Funding

Nanjing Personal Oncology Biotechnology Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

101P - HIF1-α depletion overcomes resistance to oxaliplatin in colorectal cancer via ERK signalling pathway (ID 551)

Presentation Number
101P
Lecture Time
09:00 - 09:00
Speakers
  • Se Jun Park (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemoresistance is a major reason for treatment failure and results in poor prognosis in patients with advanced colorectal cancer (CRC). Hypoxia-inducible factor-1 (HIF1-α) is a regulator of the transcriptional response to oxygen deprivation in cancer cells and activates the transcription of genes that are involved in angiogenesis, cell survival and invasion. However, the effect of HIF1-α activation on oxaliplatin resistance in CRC is unclear. This study aimed to investigate the effects and potential mechanism of HIF1-α on oxaliplatin resistance in CRC.

Methods

Oxaliplatin-resistant cells were generated from HCT116 cells. Cell Counting Kit-8, flow cytometry, Transwell assay were used to compare the characteristics of oxaliplatin resistant HCT116 (HCT116_OxR) cells and the corresponding parental HCT116 cells. The expression of HIF1-α, extracellular signal-related kinase (ERK), and transforming growth factor β (TGFβ) were confirmed by RT-PCR and western blotting in HCT116_OxR and HCT116 cells. Next, we evaluated the combination efficacy of inhibitors of HIF1-α (YC-1), ERK (Ravoxertinib), and TGFβ1 (SB431542) with oxaliplatin by in vitro and in vivo experiments.

Results

We found that cell viability of HCT116_OxR was higher than that in parental cells in the presence of oxaliplatin. The relative expression of HIF1-α was significantly increased in HCT116_OxR cells compared with the parental HCT116 cells. Downregulation of HIF1-α in HCT116_OxR cells increased oxaliplatin sensitivity, and diminished cell survival and invasion. Significantly, ERK signaling in HCT116_OxR cells is dependent on TGFβ1, promoting oxaliplatin resistance by activating HIF1-α. Inhibition of ERK by Ravoxertinib or TGFβ1 by SB431542 efficiently overcame oxaliplatin resistance in vitro and in vivo.

Conclusions

HIF1-α activation is regulated by TGFβ1/ERK axis in HCT116_OxR cells. Hence, HIF1-α, ERK, and TGFβ1 are potential therapeutic targets for overcoming oxaliplatin resistance in patients with CRC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

102P - Colorectal cancer organoids culture exploits new neoadjuvant therapy resistance mechanisms and therapeutic targets (ID 1007)

Presentation Number
102P
Lecture Time
09:00 - 09:00
Speakers
  • Yun Deng (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tumor organoids are a state of the art platform for precision medicine. With more and more studies showing that the treatment in organoids in vitro perfectly matches the patients' response, tumor organoids could predict patients' responses in clinical settings, including for colorectal cancer, pancreatic cancer, and ovarian cancer. Based on these studies, comparing the genetic data from the tumor organoids should be a strategy to investigate treatment resistance mechanisms and exploit new therapeutic targets.

Methods

Tumor organoids were obtained from our colorectal cancer organoids bank. RNA sequencing analysis was used to screen potential markers that play pivotal roles in mediating treatment response based on the organoids' response to drug treatment and radiation. Candidate genes were analyzed by qPCR, and CRISPR technology was applied to investigate the gene function in cell lines and organoids.

Results

We found several differentially expressed genes between sensitive and resistant organoid groups of which most were metabolism related. Among them, GPX2 and FREM1 were highly expressed in colorectal cancer and could prompt cell proliferation and growth. GPX2 and FREM1 are found to tightly influence treatment with 5-FU and irinotecan, respectively, in colorectal cancer cells, higher GPX2 could enhance the IC50 of 5-FU, while FREM1 increases the IC50 of irinotecan in colorectal cancer cells, and both of them could increase radiation resistance. Overexpressing GPX2 could decrease cellular ROS levels, increase stem cell marker CD24 level and EMT transition, while FREM1 could activate the NF-KB signaling and inhibit cell apoptosis included by radiation and drug treatment.

Conclusions

Tumor organoids could be useful to explore new therapeutic targets in cancer treatment with higher precision. GPX2 and FREM1 which are upregulated in colorectal cancer increase cell proliferation and growth, cause radioresistance. GPX2 is related to 5-FU resistance while FREM1 is related to irinotecan resistance in colorectal cancer cells. These results imply these two molecules could be new therapeutic targets in the treatment of colorectal cancer.

Legal entity responsible for the study

Zhen Zhang.

Funding

National Natural Science Foundation of China, 81773357.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

103P - Comprehensive genomic landscape in younger and older Chinese patients with colorectal cancer (ID 826)

Presentation Number
103P
Lecture Time
09:00 - 09:00
Speakers
  • Huina Wang (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The incidence of colorectal cancer (CRC) in young patients is increasing in recent years. However, the difference of genomic landscape between younger and older patients with CRC are poorly investigated and has never been reported in Chinese population.

Methods

A total of 75 CRC patients were enrolled. All kinds of genetic alterations were analyzed by next-generation sequencing (NGS) with Acornmed panel.

Results

Genomic landscape exhibited notable differences between younger and older CRC groups. APC and PIK3CA alterations were more commonly altered in older tumors (p < 0.05), while SMAD4 mutations tended to occur in younger tumors (p = 0.054). Notably, mutational distributions of KRAS in younger group differed from those in older group, and a higher prevalence of KRAS codon 12 alterations was potentially associated with young age (p = 0.076). Furthermore, the majority of patients (77.3%) harbored at least one clinically actionable alteration, and targeted genetic profiles between younger and older patients were significantly different (p < 0.05). Additionally, in patients with mismatch repair-proficient and mscirosatellite-stable (pMMR/MSS) CRC, tumor mutational burden (TMB) was positively correlated with age (p < 0.05), and a significantly association was found between high TMB and DNA damage response (DDR) pathway alterations (p < 0.05).

Conclusions

This study revealed different molecular profiles between younger and older Chinese patients with CRC, which provided novel insights into the personalized therapy in CRC.

Legal entity responsible for the study

Acornmed Biotechnology Co., Ltd.

Funding

Has not received any funding.

Disclosure

H. Wang, H. Cheng, T. Zhou, F. Lou, S. Cao: Full/Part-time employment: Acornmed Biotechnology Co., Ltd.

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e-Poster Display Session (ID 87) Poster Display

104P - Safety and efficacy of HLX04 versus reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment for metastatic colorectal cancer: A randomised, double-blind phase III study (ID 674)

Presentation Number
104P
Lecture Time
09:00 - 09:00
Speakers
  • Shukui Qin (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

HLX04, a proposed bevacizumab biosimilar, was developed stepwise with proven analytical and clinical PK similarities. This confirmatory ph3 study (NCT03511963) aimed to compare the safety and efficacy of HLX04 versus reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment in pts with recurrent/metastatic colorectal cancer.

Methods

We conducted this double-blind, multicentre, parallel-controlled, ph3 study (HLX04-mCRC03) in pts (18≤age≤75 years) with histologically/cytologically confirmed unresectable recurrent/metastatic CRC. Eligible subjects were randomised 1:1 to receive either HLX04 or bevacizumab intravenously (7.5 mg/kg Q3W in combination with XELOX or 5 mg/kg Q2W in combination with mFOLFOX6). The primary endpoint was the progression free survival rate at week 36 (PFSR36w) per RECIST v1.1. Secondary endpoints included ORR, 12-month OS rate and DoR. Primary and secondary endpoints were further stratified (by chemotherapy, KRAS/BARF mutation, etc.) for subgroup analyses.

Results

PFSR36w was 46.4% (n=338) in HLX04 and 50.7% (n=337) in bevacizumab per FAS. The group difference was -4.2% (90% CI -10.6%, 2.1%), which fell entirely in the pre-defined equivalence margins (-11%, 15%). No statistically significant difference was observed in primary or secondary endpoints and their subgroup analyses. Similar safety results were demonstrated between the two treatment groups. The most common TEAEs (grade≥3) in both groups were decreased neutrophil count (20.6% vs 20.2%), decreased platelet count (10.3% vs 10.1%) and hypertension (7.4% vs 12.5%). The most common SAEs in both groups were intestinal obstruction (9.0% vs 9.6%) and decreased platelet count (11.2% vs 6.7%). The incidences of death during the treatment was 11 (3.2%) and 9 (2.7%), respectively. The immunogenicity profiles were similar between treatment groups.

Conclusions

HLX04 demonstrated equivalent efficacy and similar safety and immunogenicity profiles with reference bevacizumab as first-line treatment for mCRC, presenting as an alternative option for cancer pts as a biosimilar candidate.

Clinical trial identification

NCT03511963; April 30, 2018.

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

L. Zhang, W. Li, K. Chai: Full/Part-time employment: Shanghai Henlius Biotech, Inc. W. Jiang, S. Liu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

105P - Prospective, open-label, observational study of cetuximab for metastatic colorectal carcinoma (mCRC): The OPTIM1SE study (ID 903)

Presentation Number
105P
Lecture Time
09:00 - 09:00
Speakers
  • Tsai-Sheng Yang (Taipei, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Cetuximab-based infusional 5-FU regimens are approved for the first-line treatment of mCRC in 116 countries. The OPTIM1SE study observed long-term real-world outcomes of these regimens in routine practice in Australia, South Korea, Malaysia, Singapore, Taiwan, Vietnam, Russia, Lebanon, and Saudi Arabia.

Methods

OPTIM1SE was a prospective, open-label, observational study. Patients with untreated KRAS wild-type mCRC and distant metastases were treated per the locally approved label and monitored for 3 years via hospital, laboratory, and other records. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Safety and other efficacy outcomes were secondary endpoints.

Results

From 19 Nov 2013 to 30 Jun 2016, 520 patients were enrolled by 51 sites. Patients were mostly male (61.2%) with a mean age of 58.5 (±12.0) years; 1.7% were BRAF mutated; 420 patients were treated with FOLFIRI-based regimens and 94 with FOLFOX. The most common primary tumor site was rectum (38.8%) with liver metastases (65.0%). ORR was 45.4% (95% CI, 41.1%-49.7%), including 26 patients (5.0%) with a complete response. Median progression-free survival was 9.9 months (95% CI, 8.2-11.0); median overall survival (mOS) was 30.8 months (95% CI, 27.9-33.6). Patients receiving FOLFIRI-based regimens had better outcomes than those on FOLFOX, including increased ORR (48.6% vs 34.0%) and mOS (31.3 vs 28.6 months). Higher mOS was also associated with tumors of left- rather than right-sided origin (HR 0.69 [95% CI, 0.49-0.99]), and higher ORR with liver metastases compared to all other metastases (55.4% vs 40.2%). Adverse events were consistent with the known safety profile of cetuximab. The most common treatment-related adverse events (TRAE) were rash (20.2%), dermatitis acneiform (16.5%), and paronychia (13.7%); 2.1% of patients had a serious TRAE.

Conclusions

Cetuximab-based 5-FU regimens were effective in treating patients with mCRC, particuarly in those with left-sided disease origin and with liver metastases only, in routine practice. FOLFIRI-based cetuximab regimens were more common and showed improved outcomes over FOLFOX. Our findings are consistent with recent studies.

Editorial acknowledgement

Medical editorial asssistance provided by Kristen Perry and Tim Stentiford, CMPP, of ClinicalThinking, part of Nucleus Global, and was funded by Merck Pte. Ltd.

Legal entity responsible for the study

Merck Pte. Ltd.

Funding

Merck Pte. Ltd.

Disclosure

T.W. Kim: Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Sanofi. J.B. Ahn: Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Boryung. G.F. Ho: Honoraria (self): Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AB Science; Research grant/Funding (institution): Tessa Therapeutics; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: AstraZeneca; Full/Part-time employment: University Malaya Medical Centre; Full/Part-time employment: UM Specialist Centre. L.T. Anh: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck KGaA; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis. S. Temraz: Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck KGaA; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD. M. Burge: Advisory/Consultancy: Merck KGaA. C. Chua: Research grant/Funding (institution): MSD; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Merck KGaA. J. Huang: Full/Part-time employment: Merck Pte Ltd. Y.S. Park: Advisory/Consultancy: Merck KGaA; Full/Part-time employment: Samsung Medical Center. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

106P - Efficacy and tolerability of capecitabine and mitomycin-C based concurrent radiotherapy in patients with anal canal cancer (ID 782)

Presentation Number
106P
Lecture Time
09:00 - 09:00
Speakers
  • Prabhat G. Bhargava (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Stage I-III squamous cell cancers (SCC) of the anal canal are treated with definitive concurrent chemoradiotherapy. Capecitabine (Cape) and mitomycin-C (MMC) chemotherapy is an approved concurrent regimen, but with limited evidence.

Methods

A retrospective analysis of stage I-III SCC patients treated at Tata Memorial hospital with concurrent Cape-MMC (Capecitabine 1250mg/m2 PO continuous with IV Mitomycin C 12mg/m2 on D1) based chemoradiotherapy from March 2014 to March 2020 was conducted. Patients were staged as per American Joint Committee on Cancer, seventh edition. The primary outcome of the study was recurrence-free survival (RFS). Overall survival (OS) and RFS were calculated by Kaplan-Meier estimates.

Results

Two hundred and twenty-six patients were included in the study, with the median age being 58 (range: 22-81) years. Stage I, stage II, and stage III cancers were seen in 1(0.4%), 62 (27.4%), and 163 (72.1%) patients, respectively. Patients received a median 45 Gy (range; 20-63) in 25 fractions as definitive radiotherapy with concurrent Cape-MMC. Response evaluation at 6 months was available in 190 patients, with 51 patients (27%) having local residual or progressive disease. Nine patients (4%) underwent salvage surgery. At a median follow up of 28 months, 38 recurrences had occurred, with 13 patients having only local recurrence while 25 patients had distant metastasis, with or without local recurrences. The median 2-year RFS was 82%, while median 2 years OS was 85%. Patients with stage III disease had inferior RFS as compared to patients with stage I/II disease (2 year RFS: 78% vs. 90%; p=0.042) Common grade 3 and grade 4 toxicities were local skin reactions in 44 (21.4%), neutropenia and thrombocytopenia in 9 (4.4%) patients, respectively.

Conclusions

The current study using chemoradiation with Cape-MMC is a large study in predominantly stage III anal canal cancers and shows excellent loco-regional control rates and tolerance in comparison to the traditional 5 fluorouracil-based regimens.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

107P - Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in previously treated metastatic colorectal cancer (mCRC): Results from the Australian cohort of the phase IIIb, international, open-label, early-access PRECONNECT study (ID 291)

Presentation Number
107P
Lecture Time
09:00 - 09:00
Speakers
  • Timothy J. Price (Woodville, SA, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The PRECONNECT study assessed safety and efficacy of FTD/TPI in previously treated mCRC patients in daily practice. This analysis presents the results from the Australian patient cohort.

Methods

Enrolled patients had confirmed mCRC and ECOG PS of 0 or 1, previously treated with, or not considered candidates for available therapies. Patients received FTD/TPI (35 mg/m2, orally bid, on days 1–5 and 8–12 in a 28-day cycle) with follow-up to the end of study treatment. Withdrawal criteria included disease progression, unacceptable toxicity and commercial availability of FTD/TPI. The primary endpoint was safety; secondary endpoints were PFS and QoL.

Results

70 Australian patients from 9 centres received at least one dose at cut-off (May 2018). At baseline, median age was 61 years (range 27–77); 57.1% male; 80% Caucasian, 14.3% Asian, 1.4% Black. ECOG PS was 0/1 in 54%/44%. 60% had RAS-mutant cancers; 10% had BRAF-(V600E) mutant cancers. Primaries were left-sided in 71%, right-sided in 14% (14% not specified). Over 98% received prior fluoropyrimidine and/or oxaliplatin, irinotecan, while 91%, 36% and 0% received anti-VEGF, anti-EGFR or regorafenib respectively. Most common any-grade treatment-emergent adverse events (TEAs) were nausea (49%), asthenia/fatigue (40%), neutropenia (34%), vomiting (33%), diarrhoea (26%), Anemia (21%) and constipation (20%). Most common TEAs grade ≥3 were: neutropenia (31%), anaemia (10%), diarrhoea, nausea, vomiting, abdominal pain (3%). TEAs led to patient withdrawal in 7% and dosage reduction in 9%. Median treatment duration was 3 cycles (range 1–16). Median relative dose intensity was 92%. FTD/TPI was associated with a median PFS of 2.7 months (95% CI, 2.4–3.4) and disease control rate of 40% (95% CI, 28.47–52.41). Median time to ECOG PS decline to ³2 was 14 months. Mean QLQC30 GHS at baseline was 67.2 (±17.8) with mean change from baseline to end of therapy of -11.3 (±21.7) points.

Conclusions

Results from the Australian cohort are consistent with the global PRECONNECT population and randomised datasets in previously treated mCRC patients.

Clinical trial identification

NCT03306394.

Legal entity responsible for the study

Institut de Recherches Internationales Servier.

Funding

Institut de Recherches Internationales Servier.

Disclosure

G. Tancock: Full/Part-time employment: Servier Australia Pty. Ltd. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

108P - Comparative analysis of two-stage hepatectomy and enhanced one-stage hepatectomy in the setting of bilobar colorectal liver metastases (ID 756)

Presentation Number
108P
Lecture Time
09:00 - 09:00
Speakers
  • Hayk G. Torgomyan (Nizhny Novgorod, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Multiple bilobar colorectal liver metastases (CLM) is a big challenge for surgeon oncologist due to high risk of postoperative morbidity and mortality. Two-stage hepatectomy (TSH) is a nowadays surgical standard. As alternative enhanced one-stage hepatectomy (e-OSH) with intraoperative ultrasound control to reduce the resection of the unaffected parenchyma could be performed.

Methods

665 patients with CLM who underwent liver resection at the Privolzhsky District Medical Center from 2010 to 2017 were retrospectively analyzed. Inclusion criteria were multiple CLM in one lobe with at least one lesion in the contralateral lobe. 76 patients (11,5%) were included in the study: 49 with TSH and 27 with e-OSH. Post-operative complications rate and overall survival in 2 groups were investigated and compared.

Results

Among 49 patients in first group (TSH) 23 reached to the second stage. Drop-out rate of TSH was 53%. Compared to the e-OSH patients who reached to the second stage had similar overall morbidity (TSH – 30.4% vs. e-OSH – 33.3% p = 0.827), liver-specific morbidity (TSH – 17.4% vs. e-OSH – 29.6%, p = 0.313) severe morbidity (TSH – 21.7% vs. e-OSH – 22.2% p = 0.968) and overall mortality (TSH – 8,7% vs. e-OSH – 14,8% p = 0.507). R0 resection rate was similar between groups. Completed TSH and e-OSH had similar overall survival rate (1-year 83% vs. 73% р = 0.313; 3-year 39% vs. 38% р = 0.880).

Conclusions

e-OSH may be considered as the surgical treatment of choice due to the absence of drop-out risk and a similar to TSH rate of morbidity, mortality, and overall survival. TSH is preferable to perform in cases where postoperative fatal liver insufficiency is highly likely.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

109P - Efficacy and safety of biweekly or triweekly XELOX regimen for adjuvant chemotherapy of colorectal cancer (ID 632)

Presentation Number
109P
Lecture Time
09:00 - 09:00
Speakers
  • Hangyu Zhang (hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Adjuvant CAPOX (capecitabine plus oxaliplatin) provided significant disease-free survival (DFS) benefit in patients with high-risk stage Ⅱor stage Ⅲ colorectal cancer (CRC), which might translate into long-term overall survival (OS). However, the standard triweekly CAPOX has recently raised some concerns onits hematological toxicity such as thrombocytopenia, which results in discontinuation ofadjuvant courses in a majority of patients. The regimen of modified biweekly CAPOX was observed to be generally well-tolerated in previous studies.

Methods

We conducted a prospective, phase II study to investigate the efficacy and safety between these two adjuvant chemotherapy models. Patients were randomized (1:1) to receive capecitabine 1000mg/m2 BID D1-D14 with oxaliplatin 130mg/m2 IV D1, Q21 days(standard triweekly arm) or capecitabine 1000mg/m2 BID D1-D10 with oxaliplatin 85mg/m2 IV D1, Q14 days (modifiedbiweeklyarm) as adjuvant therapy. Patients with T3N1M0 disease would receive 3 months of adjuvant chemotherapy while patients who had T4 or N2 disease would receive 6 months of adjuvant chemotherapy. The primary endpoint was DFSwhile safety and OS were secondary endpoints.

Results

Since the enrollment of the first patient on June 28, 2018, 85 patients have been enrolled, 59 of whom have completely completed adjuvant therapy, 20 patients are still in treatment, and 6 patients terminated the treatment due to personal reasons, adverse reactions intolerant or postoperative complications such as intestinal adhesion. Of the 59 patients who completed adjuvant therapy, 29 received the triweekly regimen and 30 received the biweekly regimen, respectively. Leukopenia was 43% in the biweekly group and 58% in the triweekly group. Thrombocytopenia was 33% at biweekly group, 51% at triweekly group. Peripheral neurotoxicity was 46% at biweekly group, and 75% at triweekly group.

Adverse events Grade Case No.
Biweekly XELOX Triweekly XELOX
WBC I 9 6
II 3 43% 10 58%
III 1 1
PLT I 4 7
II 3 33% 6 51%
III 3 2
Hb I 9. 36% 5 20%
II 2 1
Liver function injury I 2. 16% 5 31%
II 3 4
Peripheral neurotoxicity I 7 10
II 3 46% 5 75%
III 4 7

Conclusions

Blood toxicity was significantly reduced in the biweekly treatment group, as were liver function injury and neurotoxicity.DFS and OS are not available for the time being due to immature data.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

110P - Analysis for stereotactic body radiotherapy (SBRT) effect for colorectal liver metastases (ID 726)

Presentation Number
110P
Lecture Time
09:00 - 09:00
Speakers
  • Wei Zou (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There are various treatment methods for colorectal metastasis, such as surgery and RFA. However, not every patient is suitable for surgery, and radiofrequency ablation is a better for lesions less than 3 cm in diameter. Under this situation, SBRT can be a choice, which has the advantages of non-invasiveness and high precision. So far, there are relatively few studies on SBRT of colorectal liver metastasis worldwide and no studies have been reported in China. Therefore, this study retrospectively analyzes patients receiving SBRT treatment of colorectal liver metastasis, to explore its effectiveness and safety.

Methods

We retrospectively analyzed CRLM patients who received SBRT treatment for liver metastases from 2017 to 2019 in our center. 20 liver lesions in total were treated. Most patients (91.7%) previously received other local treatment, and Most (91.7%) patients received first-line and above systemic treatment. The median size of treated lesions is 2.5cm(1.2∼2.5cm). The average dose was 49Gy(48∼64Gy), with average fraction number of 7(5∼10) times, equals to BED as 85.5Gy(72∼115.2Gy).

Results

The median follow-up time was 15 months (range 3-22 months). 4 lesions were observed recurrence in the irradiation field. The 6-month, 1-year local control rate was 94% and 75%, if evaluated by lesion. By univariate analysis, the local control rate of liver metastases with a maximum diameter <3 cm was significantly better than that of lesions ≥ 3 cm. The 1-year local control rate was 82% and 33%, respectively, P=0.016. The patients had a median PFS of 8 months, 6 months of PFS of 58%, and 1 year of PFS of 10%. The median OS was not reached. The 6-month OS was 92%, and the 1-year OS was 73%. None of the patients had toxicity ≥ higer grade 3.

Conclusions

SBRT treatment for liver metastases from rectal cancer has shown promising local control and survival outcomes. And the local control rate of liver metastases < 3 cm in diameter was better than that of lesions ≥ 3 cm.

Legal entity responsible for the study

Fudan University Cancer Center, Shanghai, China.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

111P - A meta-analysis study on safety and effectiveness comparison between FOLFOX and XELOX regiments on advanced stage colorectal cancer (ID 871)

Presentation Number
111P
Lecture Time
09:00 - 09:00
Speakers
  • Ida Bagus Budhi (Surakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Advanced stage colorectal cancer therapy shows positive progress by increasing overall survival (OS). Mainstay treatment still uses cytotoxic agents and oxaliplatin which results in an average survival of 18 months when combined with 5-Fluorouracil (5-FU) or capecitabine. This study aims to determine the effectiveness and safety of the use of FOLFOX and XELOX chemotherapy in advanced stage colorectal cancer patients using a meta-analysis study.

Methods

This is a meta-analysis study comparing only the Randomized Controlled Trial (RCT) study using FOLFOX and XELOX chemotherapy in patients with metastatic colorectal cancer taken from PubMed, EMBASE and The Cochrane Library using keywords: Capecitabine, FOLFOX, XELOX and metastatic colorectal.

Results

9 journals were included in the inclusion criteria and were followed by a meta-analysis study. A total of 5,873 patients were obtained with the number of groups given FOLFOX of 3,034 and 2,839 in the group given XELOX. The analysis doesn’t show evidence of publication bias in the forest plot. The results of the analysis of Progress Free Survival (PFS) found no significant heterogeneity (OR = 1.09, 95% CI: 0.97-1.23, p = 0.14), the Overall Survival (OS) analysis also did not obtain heterogeneity (OR = 0.98, 95% CI : 0.87-1.10, p = 0.77). Overall Response Rate (ORR) there were no significant differences in the two groups. All studies gave grade 3 and 4 toxicity. The results of the combined analysis showed thrombocytopenia, Hand Foot Syndrome (HFS) and diarrhea in the XELOX group were significantly higher.

Conclusions

The effectiveness of XELOX and FOLFOX found no significant differences. However, the safety of the XELOX group showed significantly more side effects. Keywords: FOLFOX, XELOX, Advanced Stage Colorectal Cancer.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 89) Poster Display

112P - Pembrolizumab vs chemotherapy in patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: Asia subgroup results of the phase III KEYNOTE-177 study (ID 1048)

Presentation Number
112P
Lecture Time
09:00 - 09:00
Speakers
  • Takayuki Yoshino (Kashiwa, Chiba, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
22.11.2020
Time
09:00 - 20:00

Abstract

Background

KEYNOTE-177 (NCT02563002) was a randomized, open-label phase III study of first-line (1L) pembrolizumab (P) vs chemotherapy (C) in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). P significantly improved progression-free survival (PFS) vs C in KEYNOTE-177; the Asia subgroup (sg) analysis is presented.

Methods

Pts with previously untreated dMMR/MSI-H stage IV mCRC and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned 1:1 to P 200 mg every 3 weeks or investigator’s choice of C (mFOLFOX6/FOLFIRI every 2 weeks ± bevacizumab/cetuximab). Primary endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 by central review and overall survival. Hazard ratio and 95% confidence interval of PFS were based on Cox regression model with Efron’s method of tie handling with treatment as a covariate. PFS and duration of response (DOR) were assessed per Kaplan-Meier analysis. Secondary endpoints were overall response rate (ORR) and safety. Confirmed responses are shown.

Results

Of 307 pts enrolled in the study, 153 were randomly assigned to P and 154 to C. Of the 307 pts, 48 were enrolled from Asia (P, n=22; C, n=26). At data cutoff (19 Feb 2020), median follow-up in the Asia sg was 28.7 mo in the P arm vs 23.3 mo in the C arm. Efficacy and safety in the total population (pop) and Asia sg are presented in the table.

Conclusions

1L P compared with C showed clinically meaningful improvement in PFS, led to more durable responses and improved safety profile in the total pop of pts with dMMR/MSI-H mCRC. The Asia sg results were generally consistent with those of the total pop of KEYNOTE-177

P (total pop) C (total pop) P (Asia sg) C (Asia sg)
ITT pop, n 153 154 22 26
Median PFS, mo 16.5 8.2 NR 10.4
HR (95% CI) 0.60 (0.45-0.80) -- 0.65 (0.30-1.41) --
12-mo PFS rate, % 55.3 37.3 62.0 45.9
ORR, n (%) 67 (43.8) 51 (33.1) 10 (45.5) 12 (46.2)
CR, n (%) 17 (11.1) 6 (3.9) 2 (9.1) 3 (11.5)
PR, n (%) 50 (32.7) 45 (29.2) 8 (36.4) 9 (34.6)
Median DOR, (range), mo NR (2.3+-41.4+) 10.6 (2.8-37.5+) NR (4.4+-33.1+) 28.8 (3.4+-35.5+)
Response duration ≥24 mo, % 82.6 35.3 87.5 51.1
APAT pop, n 153 143 22 25
Any grade TRAE, n (%) 122 (79.7) 141 (98.6) 14 (63.6) 25 (100.0)
Grade 3-5 TRAE, n (%) 33 (21.6) 94 (65.7) 2 (9.1) 20 (80.0)

APAT, all patients as treated; NR, not reached; TRAE, treatment-related adverse event.

.

Clinical trial identification

NCT02563002.

Editorial acknowledgement

Provided by Jemimah Walker, PhD, and Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. Yoshino: Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Amgen K.K., Parexel International Inc., MSD K.K., Daiichi Sankyo Co., Ltd., and Sanofi K.K. T.W. Kim: Research grant/Funding (institution): Research Grant/Funding (Institution) Merk Serono, AstraZeneca, Pfizer. W.P. Yong: Speaker Bureau/Expert testimony: Bayer. K-K. Shiu: Honoraria (self): BMS, Guardant Health, Innovent Biologics, Merck KGaA, Roche, Servier; Advisory/Consultancy: Roche; Research grant/Funding (institution): Amgen, BMS, Gilead, Merck KGaA, MSD, Roche; Travel/Accommodation/Expenses: MSD, Merck KGaA, Innovent Biologics. B. Vittrup Jensen: Research grant/Funding (institution): Merck Sharp & Dohme Corp. L. Henrik Jensen: Research grant/Funding (institution): MSD, 2cureX, Incyte, BMS. R. Garcia-Carbonero: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA, Advanz Pharma, Bayer, BMS, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi and Servier; Research grant/Funding (self): Pfizer, BMS; Research grant/Funding (institution): ARMO Biosciences, AstraZeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, Bristol-Myers-Squibb, Boerhringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar; Non-remunerated activity/ies: Member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), Member of the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS), Member of the Scientific Advisory Group for Oncology (SAG-O) of th; Non-remunerated activity/ies: Global PI of a clinical trial of Axitinib (Pfizer) in NETs; Global PI of a clinical trial of Nivolumab (BMS) and chemotherapy in NECs; Non-remunerated activity/ies: Member of the EORTC, ASCO, ESMO, SEOM, TTD, GEMCAD. J. Alcaide-Garcia: Speaker Bureau/Expert testimony: Amgen; Travel/Accommodation/Expenses: MSD, Merck, Roche, Sanofi, Bristol. P. Gibbs: Honoraria (self), Research grant/Funding (self): Merck. C. de la Fouchardiere: Advisory/Consultancy: Roche, Pierre Fabre Oncologie, MSD, Eisai, Bayer; Travel/Accommodation/Expenses: Amgen, Eisai, BMS, Roche. F. Rivera: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene. E. Elez: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Hoffman La Roche, Sanofi Aventis, Amgen, Merck Serono, Servier, MSD, Array Pharmaceuticals, Bristol-Myers Squibb; Honoraria (institution): Hoffman La Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Array Pharmaceuticals, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune. J. Bendell: Research grant/Funding (institution): Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, EMD Serono, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Koltan, SynDevRex, Forty Seven, AbbVie, Ar; Advisory/Consultancy: Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Array, Sanofi, ARMO, Ipsen, Merrimack, Oncogenex, FORM; Travel/Accommodation/Expenses: Gilead, Genentech/Roche, BMS, Lilly, Merck, MedImmune, Celgene, Taiho, Novartis, OncoMed, BI, ARMO, Ipsen, Oncogenex, FORMA. D.T. Le: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Aduro, Medivir, Curegenix, Nouscom; Licensing/Royalties: Patent pending: technology for mismatch repair deficiency. P. Yang: Full/Part-time employment: MSD China Holding Co., Ltd.. M. Farooqui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. P. Marinello: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. L.A. Diaz: Advisory/Consultancy: Personal Genome Diagnostics, 4Paws, Neophore; Leadership role: Jounce Therapeutics, Personal Genome Diagnostics; Shareholder/Stockholder/Stock options: Jounce Therapeutics, Personal Genome Diagnostics, 4Paws, Amgen, Thrive; Research grant/Funding (self), Non-remunerated activity/ies: Merck; Travel/Accommodation/Expenses: Jounce Therapeutics, Personal Genome Diagnostics, 4Paws, Merck, Neophore; Licensing/Royalties: Personal Genome Diagnostics, Thrive, Qiagen; Officer/Board of Directors: Jounce Therapeutics, Personal Genome Diagnostics. T. Andre: Honoraria (self): Bristol-Myers Squibb, Chugai, GSK, Pierre Fabre, Roche/Vantana, Sanofi, Servier ; Advisory/Consultancy: Amgen, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Gritstone Oncology, Halliodx, Merck Sharp & Dohme Corp, Pierre Fabre, Roche/Vantana, Sanofi, Servier, Tesaro; Speaker Bureau/Expert testimony: Bristol-Myers Squibb, Servier; Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Travel/Accommodation/Expenses: Roche/Vantana, Merck Sharp & Dohme Corp, Bristol-Myers Squibb; Non-remunerated activity/ies: Participant to the Scientific committee of ARCAD Foundation and GERCOR Group. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

113TiP - Prospective observational study monitoring circulating tumour DNA in resectable colorectal cancer patients undergoing radical surgery: GALAXY study in CIRCULATE-Japan (ID 328)

Presentation Number
113TiP
Lecture Time
09:00 - 09:00
Speakers
  • Hiroki Yukami (Kashiwa, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Adjuvant chemotherapy has reduced the risk of recurrence and improved survival in patients with resected colorectal cancer (CRC). Early clinical utility of circulating tumor DNA (ctDNA) pre- and post-surgery has been reported across various solid tumor subtypes including CRC. Analysis of ctDNA status can be utilized as a predictor biomarker for stratifying patients based on their risk of recurrence and to monitor the effectiveness of adjuvant chemotherapy.

Trial design

GALAXY is a prospective observational study to monitor the ctDNA status and to establish the registry data in patients with stage II-IV CRC who will undergo a radical surgery. The study utilizes a personalized, tumor-informed ctDNA assay (Signatera™ bespoke multiplex-PCR NGS assay) that tracks patient-specific somatic single nucleotide variants present in plasma based on the whole-exome sequencing of tumor tissue. A total of 2500 patients will be enrolled at 146 sites and will be followed-up for 7 years. Blood samples will be collected at pre-surgery and post-surgery at 1, 3, 6, 9, 12, 18, and 24 months. Patients will also undergo regular radiologic assessment at pre-specified timepoints. Mutations in RAS, BRAF and microsatellite instability will be analyzed using PCR. The primary endpoint of the study is disease-free survival and secondary endpoints are overall survival, analysis of ctDNA status at each time point, and association between clinical characteristic and genetic alterations. Based on the ctDNA results in the GALAXY trial, patients can be enrolled either of the two distinct investigator-initiated phase III trials: the VEGA trial (treatment de-escalation) or the ALTAIR trial (treatment escalation). The VEGA trial assesses the non-inferiority of observation vs. adjuvant CAPOX in GALAXY participants who are high-risk stage II or low risk stage III CRC and show absence of ctDNA one-month post-surgery. The ALTAIR trial evaluates the superiority of FTD/TPI over placebo in GALAXY participants with ctDNA status that remains positive after the standard therapy. Moreover, additional tumor tissue and blood samples will also be banked for multi-omics analysis.

Clinical trial identification

UMIN000039205 on 01/20/2020.

Legal entity responsible for the study

CIRCULATE-Japan.

Funding

This study is funded by Japan Agency for Medical Research and Development (AMED).Grant number: JP19ck0106447.

Disclosure

D. Kotani: Honoraria (self): Takeda; Honoraria (self): Chugai; Honoraria (self): Lilly; Honoraria (self): Merck Biopharma; Honoraria (self): Taiho; Honoraria (self): Sysmex. E. Oki: Speaker Bureau/Expert testimony: Bayer Yakuhin; Speaker Bureau/Expert testimony: Chugai Pharmaceutical Co., Ltd; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co., Ltd.; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: Yakult Honsha Co., Ltd.; Speaker Bureau/Expert testimony: Merck Serono; Speaker Bureau/Expert testimony: Takeda Pharmaceutical Co., Ltd. H. Taniguchi: Honoraria (self): Takeda; Honoraria (self): Chugai; Honoraria (self): Taiho. Y. Nakamura: Research grant/Funding (self): Ono; Research grant/Funding (self): Taiho. T. Kato: Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Takeda Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Bayer Yakuhin Ltd.; Honoraria (self): Sanofi K.K.; Honoraria (self): Yakult Honsha Co. Ltd. T. Yamanaka: Honoraria (self), Research grant/Funding (self): Takeda Pharma; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Taiho Pharma; Honoraria (self), Research grant/Funding (self): Daiichi-Sankyo; Honoraria (self), Research grant/Funding (self): Ono Pharma; Research grant/Funding (self): Merck Biopharma; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (self): Bayer. A. Aleshin, P. Billings: Full/Part-time employment: Natera Inc. T. Yoshino: Research grant/Funding (self): Novartis Pharma K.K; Research grant/Funding (self): MSD. K.K.; Research grant/Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (self): Sanofi K.K.; Research grant/Funding (self): Daiichi Sankyo Company, Limited; Research grant/Funding (self): Parexel International Inc.; Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Research grant/Funding (self): GlaxoSmithKline K.K.. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO7 - Locally Advanced Rectal Cancer- A Case Report (ID 340)

Presentation Number
YO7
Lecture Time
09:00 - 09:00
Speakers
  • Uthaman Jithin (Chongqing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

-Female 61 y.o

-Rectal prolapse and hematochezia for 6 months

-BSF Scale- type 6 for half a year

-Up on DRE a mass of identified -6 cm from the anal edge

►Colonoscopy
-April 2018- Colonoscopy identified a cauliflower-like mass 6 cm from the Anal dentate line.

- Pathological diagnosis: poorly differentiated adenocarcinoma of the rectum.

►Immunohistochemistry: CK (+), P53 (+), Ki-67 (80%), CEA (-), CD20 (-)

►Pelvic Contrast-Enhanced CT- April 2018

-Thickening of the intestinal wall in the lower rectum, narrowing of the intestine and no obvious enlarged lymph nodes noted.

►Abdomen CT- Normal -CEA-17.31ng/ml,ECOG score 0

-liver and kidney function- Normal, normal ECG

►Clinical diagnosis

-Poorly differentiated adenocarcinoma in the lower rectum. Clinical stage: T4N0M0, stage IIb

►Multidisciplinary team-MDT

-Department of Radiology- The lower intestinal wall is thickened in the lower rectum, and the intestinal lumen is narrow.

-Gastrointestinal Surgery- Resectable - radical resection? Anal sphincter preservation?

-Radiotherapy-Preoperative radiotherapy

-Department of Oncology-Neoadjuvant chemoradiotherapy + surgical treatment

►First-line Treatment

-Radiotherapy- 50.4Gy/28 fractions/5.6 weeks

-Chemotherapy- (1-14 days) and(22-35 days)Tegafur 65 mg/m2

Review -June 2018 Colonoscopy

-Diagnosis: rectal mucosal chronic inflammation.

-Pathology CEA: 2.71ng/ml, liver and kidney function normal, ECOG score 0.

Pelvic CT-June 2018: thickening of the rectal wall, marginal irregularity- Evaluation of efficacy: cPR

►Surgery-July 2018:Laparoscopic radical resection of rectal cancer, sigmoid colon-rectal anastomosis

Review-6 months post-surgery: anterior sputum effusion. Carcinoembryonic antigen: 0.68 ng/ml-Efficacy: cCR

1.The best option for neoadjuvant therapy?

A.Combination chemotherapy Tegafur + oxaliplatin

B.Irinotecan

C.Bevacizumab

2.If the patient reaches cCR after neoadjuvant therapy?

A. Watch and wait

B. Postoperative radiotherapy

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e-Poster Display Session (ID 87) Poster Display

Gastrointestinal tumours, non-colorectal (ID 1146)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

122P - Nomogram to predict short-term effect of radiotherapy based on pre/post-treatment inflammatory biomarkers and their dynamic changes in esophageal squamous cell carcinoma (ID 271)

Presentation Number
122P
Lecture Time
09:00 - 09:00
Speakers
  • Shuai Liang (Jinan, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

We initial aimed to investigate pre/post-treatment inflammatory biomarkers (pre/post-IBs) and their dynamic changes (delta-IBs) on short-term effect (STE). Furthermore, a nomogram was built to provide accurate prediction of STE in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy.

Methods

The IBs included absolute lymphocyte counts (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). All pre/post-IBs and delta-IBs of 398 ESCC patients at Shandong Cancer Hospital between 2015 and 2019 were analyzed. The nomogram was then constructed that forecasted STE based on logistic regression analyses.

Results

At 1 month after radiotherapy, 261 patients (65.6%) achieved remission, and 137 patients (34.4%) achieved un-remission. The pre-ALC and pre-LMR significantly increased, pre-NLR and pre-PLR significantly decreased during radiotherapy (all P<0.001). Meanwhile, there was a positive correlation between delta-NLR as well as delta-PLR and delta-LMR (r=0.621 and 0.613, respectively), whereas a negatively correlated between delta-LMR and delta-PLR (r=-0.573). Multivariate analysis indicated that gender [OR, 0.473; 95%CI, 0.274-0.816; P=0.007], pre-ALC [OR, 0.554; 95%CI, 0.335-0.915; P=0.021], pre-NLR [OR, 3.176; 95%CI, 1.733-5.823; P<0.001], post-NLR [OR, 2.418; 95%CI, 1.271-4.600; P=0.007] and delta-NLR [OR, 1.929; 95%CI, 1.035-3.595; P=0.039] were statistically significant with STE. Nomogram for STE was established by combining all independent predictors and the concordance indexes for STE were 0.770 [95%CI, 0.719–0.820].

Conclusions

In conclusion, pre-NLR and pre-ALC, post-NLR, and delta-NLR could predict STE in ESCC patients. Further, pre-NLR had the best predictive value, and the developed nomogram with superior prediction ability for STE could assist in patients counseling and guide to make treatment decisions.

Legal entity responsible for the study

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan 250117, Shandong, People’s Republic of China.

Funding

This work was supported by the National Natural Science Foundation of China (81972864), Academic Promotion Program of Shandong First Medical University (2019RC002), Science and Technology Support Plan for Youth Innovation Teams of Universities in Shandong Province (2019KJL001) and Science and Technology Plan of Jinan (201907113).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

123P - The clinical value of prognostic nutritional index in esophagogastric junctional adenocarcinoma patients with anastomotic leakage after surgery (ID 149)

Presentation Number
123P
Lecture Time
09:00 - 09:00
Speakers
  • Yan Wang (Shijiazhuang, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To study the relationship between prognostic nutritional index (PNI) and clinicopathological factors in gastroesophageal junction cancer patients with postoperative anastomotic leakage and the clinical significance of PNI in predicting the survival of patients with postoperative anastomotic leakage.

Methods

Clinicopathological and follow-up data of 115 gastroesophageal junction cancer patients with anastomotic leakage after radical surgery in the Department of Thoracic Surgery, the 4th Hospital of Hebei Medical University from January 1 2004 to December 31 2013 were retrospectively analyzed. PNI values were calculated [PNI = absolute lymphocyte count (109/L) x 5 + serum albumin (g/L)], and was grouped according to the PNI mean value. Relationships of PNI with patient gender, age, tumor stage, tumor differentiation, tumor location, lymph node metastasis were analyzed. For survival analysis, log-rank method was used for univariate analysis, and Cox method was used for multivariate analysis.

Results

The mean PNI of patients with anastomotic leakage was 48.51 (43.25∼56.25). The 5-year survival rate of patients with PNI ≤48.51 was 58.9%, and the 5-year survival rate for patients with PNI>48.51 was 59.3%. There was no significant difference between the two groups (χ2=0.127, P=0.722). Univariate and multivariate analysis showed that N stage is an independent risk factor for the prognosis of patients with PNI≤48.51. Postoperative adjuvant treatment is an independent risk factor for the survival of patients with PNI>48.51. P for interaction between PNI and treatment modality: P=0.037.

Conclusions

The independent prognostic factors of patients with esophagogastric junction adenocarcinoma combined with anastomotic leakage are N stage and adjuvant treatment for PNI≤48.51 and PNI>48.51 group, respectively. For patients with esophagogastric junction adenocarcinoma combined with anastomotic leakage, PNI is an important factor for guiding the selection of appropriate postoperative treatment.

Legal entity responsible for the study

The Fourth Hospital of Hebei Medical University.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

124P - Prospective evaluation of pattern of care and quality of life in patients undergoing esophagectomy at a high-volume regional cancer centre in South India (ID 249)

Presentation Number
124P
Lecture Time
09:00 - 09:00
Speakers
  • Faheem A. Abdulla (Thiruvananthapuram, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Carcinoma esophagus is a disease with dismal prognosis and even though treatment has evolved considerably, morbidity after surgery has remained a drawback. We intend to prospectively study the pattern of care for such patients at our centre, how it affects their subsequent quality of life (QoL) and the factors that influence these changes.

Methods

All patients who underwent curative esophagectomy for carcinoma esophagus from May,2017 to May,2019 were included in the study after obtaining informed consent. Patient characteristics, pre-op therapy, surgical details and final histopathology reports were collected. QoL was collected at pre-op, 1 and 6 months after surgery using FACT-E, OES 18 and OG 25 questionnaires. QoL analysis was done comparing the changes that occured after curative surgery with the baseline value.

Results

99 patients underwent curative esophagectomy during the study period. With a mean age of 58.8 and a male to female ratio of 3.54 : 1, 84/99 underwent surgery after NACT. Lower third and GE junction primary adenocarcinomas accounted for 72 % of cases. Totally minimally invasive McKeowns procedure was the most common surgery done (33%). 8 patients comprised the 30-day mortality with 5 patients having anastomotic leak. QoL analysis showed a dip in post-op QoL at 1 month, with improvement to baseline at 6 months, both in general functional scales, as well as symptom scales. The improvement in symptom scales assessed by OES 18 and OG 25 were found to be statistically significant ( p value < 0.05). Younger patients (<50 yrs) and females fared better during the post-op period. There was a trend to better QoL for patients who underwent minimally invasive procedures. Those patients who had post-op complications, had inferior QoL at 1 month, but later improved by 6 months.

Conclusions

Radical esophagectomy can be performed with achievable morbidity and mortality at high volume centres. Global HRQoL scores show a dip during immediate post-surgery period, but then picks up to even eclipse pre-op values. Post-op morbidity, as expected, adversely affects HRQoL, but once patients tide over the immediate period, they often do well as time passes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

125P - Analysis of esophageal cancer incidence for last 20 years in Uzbekistan (ID 829)

Presentation Number
125P
Lecture Time
09:00 - 09:00
Speakers
  • Abrorjon A. Yusupbekov (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Esophageal cancer (EC) takes, all over the world, 9th place in the structure of new incidents of malignant tumors, amounting to 572034 registered cases and 6th place in the structure of mortality rate, taking 508585 lives annually. According to statistical data, EC develops much more often in men than in women (70% of new cases have developed in men), and people over 70 make up about 40% of the total number of cases, with a peak incidence occurring at the age of 50-60 years. However, these indicators vary by geographic region. So, for example, the highest incidence is found in East Asia, eastern and southern Africa (8.1-23.6‱), while the lowest rate belongs to central America. The aim of the research was to study the dynamics of changes in the incidence trends in the Republic of Uzbekistan over the past 20 years.

Methods

A meta-analysis of the detection of mortality of esophageal cancer (EC) for all patients with the verified diagnosis was performed. For the period from 2000 - 2019, 18129 patients were identified in the Uzbekistan and the average incidence of EC was 2.8 per 100 thousand of the population. Of these 8283 (45.7%) were treated at the clinic of NCC, in particular, 1174 (14.2%) patients were operated.

Results

The analysis revealed that in 2000, in 0,4% and 18,2% of cases, patients had I - II stage disease, in 64,5% of cases – III, and in 18,2% of cases – IV clinical stage, in 2009, 0,5% and 22,8% of cases, patients had I - II stage disease, in 54,4% of cases – III, and in 16,4% of cases - IV clinical stage, and in 2019, 3,3% and 33,7% of cases patients had I – II stage disease, in 44,5% of cases - III, and in 12,5% of cases - IV clinical stage.

Conclusions

A relative decrease in the mortality rate over the study period was also revealed: from 2.7% in 2000 to 1.8% in 2019. There has been a decrease in the mortality trend - 2000, 2009 and 2019, 2.2, 1.7 and 1.1, respectively. At the same time, 5-year survival was relatively stable and varied in the range of 12.1% - 27.3%. The largest number of patients was identified in the clinical stage III of the disease and ranged from 42.2 to 67%, respectively.

Legal entity responsible for the study

Republican Specialized Oncology and Radiology Research - Practice Medical Center (National Cancer Center).

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

126P - A phase II study of rh-endostatin combined with irinotecan plus cisplatin as the second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) (ID 604)

Presentation Number
126P
Lecture Time
09:00 - 09:00
Speakers
  • Jianhua Chang (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For patients (pts) with advanced ESCC, there is lack of effective treatment. Rh-endostatin (endostar) has shown clinical activity when combined with chemoradiotherapy in treating locally advanced ESCC. This single-arm phase II study aimed to assess the efficacy and safety of endostar combined with irinotecan and cisplatin as the second-line treatment for pts with advanced ESCC.

Methods

Eligible pts were histologically proven stage IV ESCC; 18-75 years old; had progressive disease after first line treatment or chemoradiation within a year; at least one measureable lesion according to RECIST 1.1; ECOG PS 0-1. Endostar (15 mg/m2/day, continuous infusion, day 1-7) plus irinotecan (60 mg/m2, day 1, 8) and cisplatin (60 mg/m2, day 1) were administered every 3 weeks for 4-6 cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs).

Results

From May 2017 to Jun 2020, 52 pts were enrolled and 1 patient withdrawn consent before receiving treatment, 1 patient was excluded due to concurrent radiotherapy. The mean cycle of treatment was 3.4 (range 1 to 6) in 46 patients with study discontinuation, while 4 patients remain receiving investigational treatment. Among these patients, 46 pts (90.2%) were male, and the median age was 60 (47-73). 47 pts were assessable for response. A total of 13 pts achieved partial response and 18 pts had stable disease. ORR was 27.7% and DCR was 66.0%. To date, 42 PFS events and 22 OS events have occurred. The median PFS and OS were 3.8 months (95% CI 2.4-5.3 months) and 12.3 months (95% CI 7.0-17.6 months), respectively. The most common AEs observed during this study were anemia (35.3%), neutropenia (29.4%), abdominal distension (29.4%), fatigue (27.5%), anorexia (19.6%). The most common Grade 3/4 AEs observed were neutropenia (15.7) and diarrhea (9.8%).

Conclusions

The combination of endostar plus irinotecan and cisplatin is a well-tolerated treatment option with promising activity in the second line treatment of advanced ESCC. Its efficacy and safety profile warranted further study in randomized trials.

Clinical trial identification

NCT03797625.

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

127P - A prospective phase II clinical trial exploring neoadjuvant immunotherapy combined with chemotherapy in resectable thoracic esophageal squamous cell cancer (TESCC) with multi-station lymph node metastases (NICE study): Preliminary results (ID 549)

Presentation Number
127P
Lecture Time
09:00 - 09:00
Speakers
  • Jun Liu (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients (pts) with resectable TESCC with multi-station lymph node metastases derive unoptimistic overall survival benefit with neoadjuvant or postoperative adjuvant therapy. Camrelizumab (anti-PD-1) is standard of care as second-line therapy for advanced TESCC in China. We hypothesize that the addition of camrelizumab to neoadjuvant chemotherapy agents (albumin paclitaxel and carboplatin) will increase the pathological complete response (pCR) rate compared with historical controls.

Methods

This was an investigator-initiated trial for pts with newly diagnosed AJCC 8th resectable TESCC with multi-station lymph node metastases with a plan to have surgery. Pts received 2 courses of camrelizumab 200mg IV q3w added to carboplatin AUC=5 IV q3w plus albumin paclitaxel 100 mg/m2 IV qwk with surgery 4 wks after the last dose. The primary objective was pCR. Our primary endpoint will be reached if 5/52 (9.6%) planned pts have pCR.

Results

From 11/2019 to 6/2020, 11 pts were enrolled all of whom had surgery. Median age was 65 (55-72), 9.1% women, and 36.4% PD-L1 positive (≥1%, 22C3). Pre-surgical grade 3/4 toxicity occurred in 8/11pts, and treatment was delayed by an average of 5.7 days due to toxicities. Grade 3/4 toxicities were neutropenia (8/11), thrombocytopenia (2/11). All pts recovered well from pre-surgical toxicities.Our primary endpoint was met; the pCR (pT0N0M0) was achieved in 45.4% (5/11) and pT0 was 54.5% (6/11). Radiologic response rate was 90.9% (PR10,CR0). Pts with either PD-L1+ or PD-L1- had pCRs. R0 resection rate was 100% (11/11). The average intraoperative blood loss was 172ml and the average hospitalization time after operation was 9 days (7-12days).No patient developed anastomotic leak and died due to treatment-related toxicity.

Conclusions

The addition of camrelizumab to neoadjuvant chemotherapy agents (albumin paclitaxel and carboplatin) was well tolerated. The primary endpoint of pCR in at least 5/52 pts was surpassed with pCR in 5/11 pts post-surgery. The pCR was seen independent of PD-L1 score. The surprisingly good preliminary results have encouraged us to keep this phase II study ongoing.

Clinical trial identification

ChiCTR1900026240.

Legal entity responsible for the study

Shanghai Chest Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

128P - Clinical update with plasma and tumour-based genomic analyses in expansion part of phase I study of selective FGFR inhibitor E7090 (ID 391)

Presentation Number
128P
Lecture Time
09:00 - 09:00
Speakers
  • Chigusa Morizane (Chuo-ku, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The first-in-human phase I study of E7090 consists of dose-escalation (Part 1) and expansion (Part 2) cohorts, which has been conducted in Japan. The interim analysis results of Part 2, as of 31 July 2019, were reported (ASCO-GI 2020 #538). The interim analysis indicated that E7090 had a manageable safety profile and the promising clinical activity in cholangiocarcinoma subjects with FGFR2 rearrangements. In this study, we analyzed tumor tissue and plasma samples with NGS panels to assess baseline tumor gene characteristics and evolution of the ctDNA profile during E7090 treatment.

Methods

In part 2, subjects with cholangiocarcinoma harboring FGFR2 gene rearrangements (cholangiocarcinoma [CCA] cohort) and gastric cancer harboring FGFR2 gene amplification or FGFR2 protein high expression (GC cohort) were enrolled. Archival tumor tissue samples were analyzed with PGDx elio tissue complete NGS panel (PGDx; Personal Genome Diagnostics, Inc.). Plasma sample was collected at pre-treatment, every day 1 of odd cycle on-treatment and at discontinuation visit for ctDNA analysis with PGDx elio plasma resolve NGS panel.

Results

As of cutoff date, 3 June 2020, 6 subjects harboring FGFR2 rearrangements identified with break-apart fluorescence in situ hybridization were enrolled in the CCA cohort. Among six tumor tissue samples, one was failed in quality-check of NGS assay. Fusion gene partner in FGFR2 rearrangements was identified in 4 of the 5 tumor tissues as BICC1, CCDC6, POC1B, and SLMAP (n=1, each). FGFR2 rearrangements were also detected in baseline blood samples from 3 of the 6 subjects. In those three cases, the number of mutant reads for FGFR2 rearrangements in ctDNA assay decreased during treatment. ctDNA for FGFR2 (L617F, M537I) were detected in blood from 2 subjects at discontinuation visit. The updated efficacy and safety results in Part 2 will also be presented as of a new cutoff date.

Conclusions

The NGS assay illuminated FGFR2 fusion partners in archival tumor tissues. Besides, ctDNA analysis indicated ctDNA for FGFR2 rearrangements were decreased during E7090 treatments, and the potential clonal changes occurred as detections of ctDNA with FGFR2 mutations.

Clinical trial identification

NCT02275910.

Legal entity responsible for the study

Eisai.

Funding

Eisai.

Disclosure

C. Morizane: Honoraria (self): MSD K.K., Yakult Honsha, Novartis, Eisai, Teijin Pharma, Taiho Pharmaceutical; Research grant/Funding (institution): Yakult Honsha, Eisai, Taiho Pharmaceutical, Merck Biopharma, AstraZeneca, J-Pharma; Advisory/Consultancy: MSD K.K., AbbVie, Novartis, AstraZeneca,. M. Ueno: Honoraria (self): Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Ono Pharmaceutical, Merck Biopharma, MSD; Research grant/Funding (institution): Taiho Pharmaceutical, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Biopharma, Dainippon Sumitomo Pharma, Incyte, Yakult Honsha, Astellas. T. Ioka: Honoraria (self): Taiho Pharmaceutical, Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Otsuka; Advisory/Consultancy: Taiho Pharmaceutical, Otsuka, Shire, Daiichi Sankyo; Research grant/Funding (institution): AstraZeneca, Dainippon Sumitomo Pharma, Baxalta/Shire, Eisai, Taiho Pharmaceutical, Taiho Pharmaceutical, Incyte, Takara Bio; Research grant/Funding (self): Taiho Pharmaceutical. M. Tajika: Speaker Bureau/Expert testimony: EA Pharma Co., Ltd., Olympus. M. Ikeda: Research grant/Funding (institution): Aslan Pharmaceuticals; Honoraria (self): Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Bristol-Myers Sqiibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Micron; Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self), Advisory/Consultancy: Nihon Seriver; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis Pharma; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self): Mylan, Otsuka Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical, Teijin Pharma; Advisory/Consultancy: Takeda. K. Yamaguchi: Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo; Honoraria (institution), Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau/Expert testimony: Chugai Pharm; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Honoraria (institution), Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Honoraria (institution), Speaker Bureau/Expert testimony: Lilly; Honoraria (institution), Speaker Bureau/Expert testimony: Sanofi; Honoraria (institution): MSD oncology; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult Honsha. H. Hara: Advisory/Consultancy: Lilly, MSD, Ono: Honoraria (institution): Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Merck Biopharma, MSD, Ono, Sanofi, Taiho, Takeda and Yakult; Research grant/Funding (institution): Astellas, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Incyte, LSK BioPharma, Merck Biopharma, MSD, Ono, Pfizer, Taiho. A. Miyamoto: Research grant/Funding (institution): Eisai. S. Iwasa: Research grant/Funding (institution): Eisai, BMS, Daiichi-Sankyo, Ono, Bayer, Pfizer, Astellas; Honoraria (self): BMS, Ono, Chugai, Taiho. M. Muto: Research grant/Funding (institution): Eisai. T. Takashima: Honoraria (self): Taiho Pharmaceutical Co., Ltd; Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): Daiichi-Sankyo K.K. K. Minashi: Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd; Research grant/Funding (institution): Daiichi Sankyo Company, Limited. Y. Komatsu: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi-Sankyo, Yakult, Chugai, Taiho, Lilly, Sanofi, Ono, Nipro, Asahikasei, Nihonkayaku, Takeda; Research grant/Funding (institution): Eisai, MSD; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self): Kyowa Kirin, Merck Biopharma, Bristol-Myers Squibb, Shire Japan, Novartis Pharma, Pfizer, Mitsubishi Tanabe, Otsuka; Research grant/Funding (self): A2 Healthcare Corp., Astellas Pharma, Dainippon Sumitomo Pharma, NanoCarrier, Parexel International Corporation, IQVIA Inc., Syneos Health Clinical, Sysmex Corporation. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Merck biopharma; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Suibb; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo; Research grant/Funding (institution): Eisai; Honoraria (self): Nihonkayaku; Honoraria (self): Yaklut Honsya. T. Nakajima: Honoraria (self): Mochida Pharmaceutical, Celltrion Healthcare Japan, Merck Serono Co., Sawai Pharmaceutical Co., Bayer Yakuhin, Bristol-Myers Squibb, Teijin Pharma, Pfizer Japan Inc., Novartis Japan, Yakult Honsha Co., Nipro Co.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Sanofi K.K., Daiichi Sankyo Co., Eli Lilly Japan K.K., Nippon Kayaku Co., Ono Pharmaceutical Co., MSD K.K.; Research grant/Funding (institution): Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Eisai Co., Solasia Pharma K.K. T. Sahara: Full/Part-time employment: Eisai. S. Funasaka: Full/Part-time employment: Eisai. M. Yashiro: Research grant/Funding (self): Eisai Co., Ltd.; Research grant/Funding (self): Daiichi Sankyo Co., Ltd.; Research grant/Funding (self): Chiome Bioscience Inc.; Research grant/Funding (self): Five Prime Therapeutics, Inc. J. Furuse: Honoraria (self): Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin Pharma, Shionogi, EA Pharma, Eli Lilly Japan, Takeda, Chugai Pharma, Fujifilm, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobel p; Research grant/Funding (institution): Eisai, Fujifilm, Ono Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly Japan, Astellas Pharma, AstraZeneca, AbbVie, Shire, Merck Serono, Takara Bio, Chugai Pharma, Bayer Yakuhin, Otsuka, Novartis, MSD, Sumitomo Dainippon, J-Pharma. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

129P - Exploration of the best candidates for splenic hilar lymph node dissection (No.10 LND) based on long-term survival: Stage IIIA proximal gastric cancer may benefit from No.10 LND (ID 453)

Presentation Number
129P
Lecture Time
09:00 - 09:00
Speakers
  • Zu-Kai Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There is no conclusion regarding the indications for No.10 LND in advanced proximal gastric cancer (PGC). We aimed to explore the best candidates for splenic hilar lymph node dissection (No.10 LND) from the perspective of long-term survival.

Methods

Data of 995 patients who underwent laparoscopic radical gastrectomy from January 2008 to December 2014 were analyzed. Five hundred sixty-four patients underwent No.10 LND (No.10D+ group); the other 431 patients did not receive No.10 LND (No.10D- group). Propensity score matching was applied to reduce the effects of observed confounding. Study end points were overall survival (OS) and disease-free survival (DFS).

Results

No.10 LN metastasis was associated with pT or pN in multivariate logistic analysis (P<0.05). Recursive partitioning analysis obtained 3 groups of patients with different risks of No.10 LN metastasis: low-risk group (pT1-3N0-1), the No.10 LN metastasis rate was 0; intermediate-risk group (pT4aN0-1, pTanyN2, pT1-3N3a), the rate was 6.5%; and high-risk group (pT1-3N3b, pT4aN3), the rate was 30.5%. After matching, stepwise stratification survival analysis showed that for stage IIIA PGC, the No.10D+ group had significantly better survival than the No.10D- group (5-year OS: 68.9% vs. 48.1%%, P=0.001; 5-year DFS: 66.3% vs. 41.2%, P=0.001). Comparison of recurrence patterns in stage IIIA PGC showed that the No.10D+ group had a significantly lower overall recurrence rate (26.4% vs. 50.6%, P=0.004) and distant metastasis rate (11.1% vs. 38.1%, P<0.001) than the No.10D- group.

Conclusions

Stage IIIA PGC may achieve the benefit of long-term survival from No.10 LND. For PGC with stage IIIB and IIIC, although the No.10 LN metastasis rate is high, No.10 LND does not result in survival benefits, and neoadjuvant therapy before surgery is recommended.

Legal entity responsible for the study

The authors.

Funding

Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

130P - Reappraisal of the role of no. 10 lymphadenectomy for proximal gastric cancer in the era of minimal invasive surgery during total gastrectomy: A pooled analysis of 4 prospective trials (ID 466)

Presentation Number
130P
Lecture Time
09:00 - 09:00
Speakers
  • Qing Zhong (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it.

Methods

A total of 1068 patients (D2 group=409; D2+No. 10 group=659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed.

Results

No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2+No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size >5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2+No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations.

Conclusions

LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

131P - Prognostic value of tumour regression grading (TRG) in patients treated with neoadjuvant chemotherapy plus surgery for gastric cancer (ID 500)

Presentation Number
131P
Lecture Time
09:00 - 09:00
Speakers
  • Jian-Wei Xie (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The factors associated with a better tumor response rate and an optimal neoadjuvant chemotherapy regimen are uncertain. We aimed to validate the prognostic value of tumor regression grading (TRG) and explore the associated factors of TRG for advanced gastric cancer (AGC) with neoadjuvant chemotherapy (NACT) plus surgery.

Methods

Three hundred forty-four AGC patients treated with NACT followed by gastrectomy at the Mayo Clinic, USA and the Fujian Medical University Union Hospital, China between January 2000 and December 2016 were enrolled in this study. Cox regression was used to identify covariates associated with overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to reveal factors predicting the tumor regression grading.

Results

For patients with TRG 0-1, the 3- and 5-year OS rates were 85.2% and 74.5%, respectively, when compared to 56.1% and 44.1% in patients with TRG 2 and 28.2% and 23.0% in patients with TRG 3, respectively(p=0.000). TRGs were independent risk factors for OS. Similar findings were observed in RFS. The oxaliplatin-based regimen was superior to the non-oxaliplatin-based regimen for the OS (38.4m vs 19.5m, respectively; p=0.01). Subgroup analyses by histological subtype indicated that the oxaliplatin-based regimen improved the OS in non-signet ring cell carcinoma compared to the non-oxaliplatin-based regimen (53.7m vs 19.5m, respectively; p=0.011). However, Similar findings were not observed in RFS.

Conclusions

TRG was an independent factor of AGC treated with neoadjuvant chemotherapy plus surgery. Oxaliplatin-based neoadjuvant chemotherapy regimens improve tumor response and may have an overall survival benefit for patients with non-signet ring cell carcinoma.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

132P - Impact of increasing age on cancer- and noncancer-specific mortality in patients with gastric cancer treated by radical surgery: A competing risk analysis (ID 505)

Presentation Number
132P
Lecture Time
09:00 - 09:00
Speakers
  • Long-Long Cao (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To perform competing risk analysis and evaluate cancer- and noncancer-specific mortality in patients with gastric cancer after radical surgery.

Methods

A total of 5051 patients from our department (as training set) and a total of 7123 patients from the Surveillance, Epidemiology, and End Results (SEER) database (as validation set) were enrolled in the study. The cumulative incidence of cancer and noncancer-specific mortality was determined by univariate and multivariate competing risk analysis.

Results

The five-year cancer- and noncancer-specific cumulative incidence of death (CID) in the training set were 36.9% and 2.5%, respectively, which were significantly lower than that in the validation set (48.2% and 8.6%, respectively). Multivariable analysis showed that age, tumor site, tumor size and pTNM stage were independent predictors of gastric cancer-specific mortality and overall survival, whereas age was an independent predictor of gastric noncancer-specific mortality. Noncancer–specific CID surpassed cancer-specific CID for pTNM stage I patients after approximately 8 years of surgery, but never for stage II and III patients. Moreover, for stage I patients, the time point when noncancer–specific CID surpassed cancer-specific CID become earlier as age increasing, with only 3.5 years after surgery for patients more than 74 years of age.

Conclusions

Age is an independent predictor of gastric cancer- and noncancer specific mortality and overall survival for patients after radical surgery. For patients with stage I gastric cancer, noncancer-specific mortality is a significant competing event, with an increasing impact as age increases.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

133P - Which patient subgroup needs more attention in early treatment failure? A matched cohort study of treatment failure patterns in locally advanced gastric cancer (ID 692)

Presentation Number
133P
Lecture Time
09:00 - 09:00
Speakers
  • Dong Wu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The aim of this study was to compare the treatment failure patterns after laparoscopic (LG) and open gastrectomy (OG) in locally advanced gastric cancer (LAGC).

Methods

A total of 1792 LAGC patients who underwent radical resection between January 2010 and December 2016 were divided into an LG group (n=1557) and OG group (n=235). Propensity score matching was performed to balance the two groups. Dynamic hazard rates of failure were calculated using the hazard function.

Results

A total of 1175 LAGC patients were included after matching (LG group, n=940; OG, n=235). The treatment failure rate of the whole group was 43.23% (508/1175), accounting for 41.38% (389/940) and 50.64% (119/235) in the LG and OG groups, respectively. The static treatment failure pattern showed that only distant recurrence rate of the LG group was significantly lower than that of the OG group (22.02% vs. 28.94%, P=0.025). Landmark analysis showed a lower early treatment failure rate of the LG group in stage Ib-IIIb subgroup (P=0.004). Furthermore, dynamic hazard curve peaked at 9.4 months (Peak rate=0.0186) and then gradually declined. For stage Ⅰb to Ⅲb patients, time of peak failure hazard was 5.2 months earlier in the OG group (OG versus LG: 11.0 versus 16.2 months). Finally, LG was an independent protective factor associated with early treatment failure in stage Ib-IIIb patients (hazard ratio, 0.63; 95% CI, 0.43-0.93; P=0.019).

Conclusions

Given the differences in treatment failure patterns between LG and OG, shorter-interval surveillance for the first 2 years should be considered for stage Ib-IIIb patients after OG.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

134P - Effect of preoperative tumour under-staging on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (ID 700)

Presentation Number
134P
Lecture Time
09:00 - 09:00
Speakers
  • Mi Lin (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study aimed to evaluate the effect of preoperative tumour staging deviation (PTSD) on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (RGGC).

Methods

Clinicopathological data of 2 346 patients who underwent RGGC were retrospectively analysed. The preoperative tumour-lymph node-metastasis (TNM) under-staging group (uTNM) comprised patients who had earlier preoperative TNM than postoperative TNM, and the no preoperative under-staging group (nTNM) comprised the remaining patients.

Results

There were 1 031 uTNM (44.0%) and 1 315 nTNM cases (56.0%). Cox prognostic analysis revealed that PTSD independently affected the overall survival (OS) after surgery. The 5-year OS was lower in the uTNM group (41.8%) than in the nTNM group (71.6%). Analysis of surgical and pathological factors showed that among patients with pT2, pT3+4, and pN+, all patients in group nTNM underwent D2 lymph node dissection (LND), whereas 15.1%, 1.3%, and 5.5% patients in group uTNM underwent D1 + LND, respectively. Among patients with pN0, the lymph node noncompliance rate was higher in the uTNM than in the nTNM group. Logistic analyses revealed that high BMI, tumour size <2 cm, early gross typing, and differentiated tumours in the upper stomach independently affected uTNM (P < 0.05).

Conclusions

Underestimated tumour staging is not rare, which possibly results in inadequate LND and affects the long-term survival for patients undergoing RGGC. D2 LND should be carefully performed in patients who are predisposed to this underestimation.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

135P - Significance of lymphatic invasion in the indication for additional gastrectomy after endoscopic treatment (ID 169)

Presentation Number
135P
Lecture Time
09:00 - 09:00
Speakers
  • Hirohito Fujikawa (Yokohama, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In latest Japanese guidelines for gastric cancer treatment, the curability of endoscopic resection of patients with lymphovascular invasion (LVI) is classified as C-2 regardless of the presence or absence of other risk factors, and the standard therapy for C-2 is additional radical resection. On the other hand, pathological diagnosis after additional resection is often diagnosed as pN0, resulting in over treatment. The aim of this study was to investigate the clinical significance of LVI in the indication of endoscopic resection for gastric cancer, and also to evaluate the recently proposed stratification using the eCura system, a new scoring system for post-ESD curability of early gastric cancer.

Methods

A total of 164 patients who underwent additional surgical resection after endoscopic resection were enrolled in this study. The correlation between LVI and pathological lymph node metastasis was investigated and compared with the eCura system score.

Results

Patients with LVI positive (LVI (+)) were 64, and 100 were LVI negative (LVI (-)). Only 12 (7.3%) had lymph node metastasis, 8 (12.5%) in the LVI (+) and 4 (4.0%) in the LVI (-) (p = 0.04). In 9 cases, additional resection was indicated only by LVI, and none of the lymph node metastases was observed. The risk assessment using eCura system for all cases were low / intermediate / high risk: 103 (62.8%) / 42 (25.6%) / 19 (11.6%). The positive rate of lymph node metastasis was 4 (3.9%) / 4 (9.5%) / 4 (21.1%) respectively. Of the 9 cases resected by LVI alone, there were no cases classified as high risk.

Conclusions

Indications for additional surgical resection based on LVI alone are likely to be over treatment, and in such cases, careful judgment is required with reference to evaluation by the eCura system.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

136P - Modified ypTNM staging classification for gastric cancer after neoadjuvant therapy: A multi-institutional study (ID 705)

Presentation Number
136P
Lecture Time
09:00 - 09:00
Speakers
  • Wen-Wu Qiu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the AJCC Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging.

Methods

Clinicopathological data of 1791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the SEER database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th ypTNM staging and the modified staging for patients after neoadjuvant therapy.

Results

In the development cohort, the 5-year OS for AJCC stage I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stage IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p < 0.001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p < 0.001), predictive accuracy (mean difference in BIC: 64.94; NRI: 35.54%; IDI: 0.032, all p<0.001), and model stability (time-dependent ROC curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p<0.05).

Conclusions

We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th ypTNM staging, allowing more accurate assessment of the prognosis of GC patients after neoadjuvant therapy.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

137P - Clinical utility of circulating tumour DNA (ctDNA) in resectable gastric cancer (GC) (ID 974)

Presentation Number
137P
Lecture Time
09:00 - 09:00
Speakers
  • Mikhail Fedyanin (Moscow, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Circulating tumor DNA (CtDNA) has shown its negative prognostic value in a number of studies, however, data on the role of ctDNA in resectable gastric cancer (GC) are lacking. The aim of our study was to determine the prognostic value of ctDNA at various stages of the disease using our simple and cheap test.

Methods

This prospective study included patients with diagnosis of GC who received treatment from 2017 to 2019. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored by ddPCR in plasma samples taken before and after surgery in case of resectable GC (n=42) and before and during chemotherapy in case of advanced GC (n=13). The median time between surgery and blood sampling was 7 days (5-15 days, σ 2.3). The plasma sample was considered "positive” if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma.

Results

Tumor-derived mutations were found in plasma with sensitivity of 74.5% (n=55): in stage IV (n=13) – 92.3%, stage III (n=24) – 70.8%, stage II (n=11) – 81.8% and in stage I (n=7) – 100%. In the group with resectable GC 24 (57.1%) pts received adjuvant or perioperative chemotherapy. Detection of ctDNA before surgery did not affect DFS (HR 0.7, 95%CI 0.04-11.5, p=0.8). In 10 (23.8%) cases ctDNA was determined after surgery. Progression of the disease was detected in 6/10 (50%) pts with ctDNA(+) and 6/32 (18.8%) - in ctDNA(-) pts (p = 0.012). One-year DFS in ctDNA(+) and ctDNA(-) pts with resectable GC after surgery were 25.4% and 73.2%, respectively. ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 6.6, 95%CI 1.5-30, p =0.014).

Conclusions

A robust and economical assay of ctDNA detection is sensitive and demonstrates the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the GC. Further clinical validation of this approach is required in trails with modifications of the perioperative treatment, in terms of escalation and de-escalation, according to the content of ctDNA.

Legal entity responsible for the study

The authors.

Funding

This research is conducted under the auspices of the experimental governmental assignment of the Ministry of Health of the Russian Federation and coordinated by the FSBI “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Ministry of Health of the Russian Federation.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

138P - Prognostic importance of dynamic changes in systemic inflammatory markers for patients with gastric cancer (ID 428)

Presentation Number
138P
Lecture Time
09:00 - 09:00
Speakers
  • Ying-Qi Huang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Systemic inflammatory markers (SIM) are closely related to the prognosis of various tumors. However, most of the studies were mainly limited to examining the preoperative level of these markers to evaluate prognosis. Reports on the significance of postoperative SIM in predicting the long-term prognosis of gastric cancer (GC) were rare. Therefore, this study aims to explore the preoperative and postoperative longitudinal changes of SIM in patients with GC and the impact on long-term prognosis.

Methods

The prospectively collected data from 2180 patients with GC who underwent radical gastrectomy between January 2009 and December 2014 at Fujian Medical University Union Hospital (FMUUH) were retrospectively analyzed. Changes in SIM between preoperatively and 1-6 months and 12 months postoperatively were reported. Cox univariate and multivariate analyses were performed to determine the prognosis of GC.

Results

In multivariate analysis, higher preoperative systemic inflammation score (pre-SIS) was independent predictor of poor prognosis (P <0.05). Further analysis showed that the area under the curve (AUC) of pre-SIS for prediction of 5-year overall survival (OS) was highest [0.605 (95% CI 0.584-0.6250)]. The optimal time of remeasurement was 12 months postoperatively, based on a longitudinal profile of SIS and accuracy in predicting 5-year OS [AUC: 0.712 (95% CI 0.630 - 0.785)]. According to the association between the conversion of SIS and OS, we classified patients into three risk groups. Kaplan-Meier (K-M) curves showed significant differences in OS among risk groups. Further Cox multivariate regression analysis showed that only risk groups of SIS and pTNM stage were independent prognostic factors for OS.

Conclusions

The efficacy of SIS in predicting prognosis 12 months after surgery is superior, and the elevation of SIS 12 months after surgery predicts poor prognosis. These findings provide support for the remeasurement of SIS 12 months after surgery.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

139P - An intraoperative model for predicting survival and deciding therapeutic schedules: A comprehensive analysis of peritoneal metastasis in patients with advanced gastric cancer (ID 474)

Presentation Number
139P
Lecture Time
09:00 - 09:00
Speakers
  • Zhi-Yu Liu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

No specialized prognosis model for gastric cancer patients with peritoneal metastasis (GCPM) exists for intraoperative clinical decision-making. This study aims to establish a new prognostic model to provide individual treatment decisions for GCPM.

Methods

This retrospective analysis included 324 GCPM diagnosed pathologically by laparoscopy from January 2007 to January 2018 who were randomly assigned to different sets (227 in the training set and 97 in the validation set). A nomogram was established from preoperative and intraoperative variables determined by the Cox model. The peritoneal metastasis nomogram (PMN), was compared with the 15th peritoneal metastasis staging system (P1abc) for its predictive ability and clinical applicability.

Results

The median survival time was 8 (range, 1-90) months. In the training set, each PMN substage had significantly different survival curves (P<0.001), and the PMN was superior to P1abc based on the results of time-dependent receiver operating characteristic curve, C-index, Akaike information criterion and likelihood ratio chi-square analyses. In the validation set, the PMN was also better than P1abc in terms of its predictive ability. Of the PMN1 patients, those undergoing palliative resection (PR) had better OS than those undergoing exploratory surgery (ES) (P<0.05). Among the patients undergoing ES, those who received chemotherapy exhibited better OS than those who did not (P<0.05). Among the patients with PR, only PMN1 patients exhibited better OS following chemotherapy (P<0.05).

Conclusions

We developed and validated a simple, specific peritoneal metastasis model for GCPM that can predict prognosis well and guide treatment decisions.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

140P - Preoperative and postoperative C-reactive protein levels predict recurrence and chemotherapy benefit in gastric cancer (ID 693)

Presentation Number
140P
Lecture Time
09:00 - 09:00
Speakers
  • Li-Li Shen (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Preoperative and postoperative C-reactive protein (CRP) levels are related to the prognosis for cancer patients. This study aimed to explore the predictive value of combining the two in gastric cancer (GC) patients.

Methods

Patients in a clinical trial (NCT02327481) from January 2015 to April 2016 were analyzed. Receiver operating characteristic curves (ROCs) were generated. By calculating the areas under the curve (AUC) and the C-index, the discriminative ability of CRP during different periods were compared, including preoperative (pre-CRP), postoperative days 1, 3, and 5 (post-CRPs) and postoperative maximum CRP (post-CRPmax).

Results

Ultimately, 401 patients were included in this study. The median follow-up time was 42 months (range 3-51 months). For postoperative recurrence, the AUC and C-index of pre-CRP were 0.692 and 0.678, respectively, higher than those for post-CRPs, all p<0.05. Among post-CRPs, post-CRPmax had the highest AUC (0.591) and C-index (0.585). The optimal cut-off values for pre-CRP and post-CRPmax were 3.1mg/L and 77.1mg/L, respectively. Multivariate analysis showed both pre-CRP≥3.1mg/L (high-pre-CRP) and post-CRPmax≥77.1mg/L (high-post-CRPmax) were independent factors for recurrence-free survival (RFS). The model consisting of the pre-CRP, post-CRPmax and TNM had higher predictive ability and clinical utility. Adjuvant chemotherapy (ACT) benefit analysis for stage II/III GC showed patients with pre-CRP<3.1mg/L did not benefit from chemotherapy (RFS:90.0% nonchemotherapy group vs 80.7% chemotherapy group, p=0.557). In the high-pre-CRP group, only patients with high-post-CRPmax but not post-CRPmax<77.1mg/L benefited from chemotherapy (RFS:33.2% nonchemotherapy group vs 49.9% chemotherapy group, p=0.037). Similar findings were observed for overall survival.

Conclusions

Both pre-CRP and post-CRPmax, inexpensively and easily obtained, are independent predictors of recurrence for GC. ACT significantly prolonged the RFS for stage II/III GC with high-pre-CRP and high-post-CRPmax after R0 resection.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

141P - Low expression of CDK5RAP3 and UFM1 indicates poor prognosis in patients with gastric cancer (ID 706)

Presentation Number
141P
Lecture Time
09:00 - 09:00
Speakers
  • Ning-Zi Lian (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the correlation between different expression of CDK5RAP3 and UFM1 and the long-term survival of patients undergoing radical gastrectomy.

Methods

The expression of CDK5RAP3 and UFM1 in cancer and adjacent tissues of gastric cancer patients were detected, and their relationship with clinical pathological parameters and long-term prognosis were analyzed.

Results

Low expression of CDK5RAP3 was detected in 102 patients (78.5%), and UFM1 expression was low in 99 patients (76.2%), and the expression of the two was significantly positively correlated. Based on the co-expression of CDK5RAP3 and UFM1, we found that the low expression of CDK5RAP3 and UFM1 was closely related to the depth of invasion (P = 0.041), lymph node metastasis (p = 0.006), and TNM stage (P = 0.000). In Kaplan-Meier analysis, the prognosis of patients with low expression of CDK5RAP3 and UFM1 was significantly poorer than that of patients with high expression of CDK5RAP3 or UFM1 (p = 0.005), and could be used as an independent risk factor for the prognosis of the entire group of patients. The co-expression of CDK5RAP3 and UFM1 had the largest area under the ROC curve, and the patients’ long-term prognosis was better than the TNM stage alone, and has statistical significance (p <0.05).

Conclusions

The expressions of CDK5RAP3 and UFM1 are significantly reduced in gastric cancer tissues. The co-expression of CDK5RAP3 and UFM1 is an independent prognostic factor for gastric cancer. Combining the expression of the two can provide a more accurate prognostic model for predicting the overall survival of gastric cancer.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

142P - Prognostic analysis of patients with intra-abdominal infectious complications after laparoscopy and open radical gastrectomy for gastric cancer: A propensity score-matching analysis (ID 703)

Presentation Number
142P
Lecture Time
09:00 - 09:00
Speakers
  • Si-Jin Que (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the incidence and prognosis of intra-abdominal infectious complications (IaIC) after laparoscopic and open radical gastrectomy for gastric cancer.

Methods

The data of patients who underwent radical gastrectomy for gastric cancer at the Fujian Medical University Union Hospital from January 2000 to December 2014, retrospectively LAG and OG were used. 1:1 propensity score matching (PSM) was used to reduce biases. The incidence and prognosis of postoperative IaIC in the two groups were analyzed.

Results

The incidence of IaIC after OG and LAG was 4.1% and 5.1%, respectively(p=0.264). Cox multivariate analysis showed that IaIC was an independent risk factor for overall survival (OS) of patients undergoing gastrectomy (HR: 1.65, 95%CI: 1.23-2.20, p<0.001). Analysis also showed that LAG was an independent protective factor for OS with IaIC (HR 0.54, 95%CI: 0.31-0.96, p=0.036), and tumor diameter ≥ 50 mm (p=0.01) and pTNM III stage (p<0.001) were independent risk factors. After PSM, the five-year OS rate of patients with IaIC in the LAG was higher than that in the OG (51.1% vs. 32.4%, p=0.042). The independent preoperative risk factors for IaIC include male (OR 1.82, p=0.046) and BMI ≥ 25 (OR 1.88, p=0.021). Among patients with IaIC, the prognostic nutritional index (PNI) in OG group was similar to that in LAG group before operation (p=0.220), but lower than that in LAG group on the 1st, 3rd, and 5th day after surgery (p<0.05).

Conclusions

Compared to OG, LAG can improve the prognosis of patients with postoperative IaIC. For high-risk patients with IaIC, LAG is recommended.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

143P - Lymph nodes metastasis is the most important factor associated with pattern of recurrence following curative resection of gastric adenocarcinoma (ID 488)

Presentation Number
143P
Lecture Time
09:00 - 09:00
Speakers
  • Fu-Hai Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lymph node status is among the most important predictors of recurrence after curative gastrectomy. However, the impact of lymph node status on recurrence patterns remains unclear. We aimed to analyse recurrence patterns in completely resected gastric cancer (GC) with negative (pN0) or positive (pN+) lymph nodes.

Methods

We retrospectively assessed 1694 patients who underwent curative gastrectomy from January 2010 to August 2014. Patients were divided into pN0(n=655) and pN+(n=1039) cohorts. Timing and site(s) of recurrence were examined.

Results

Of all,517(30.5%) patients developed recurrent disease, and complete data on recurrence could be obtained in 493 patients.For the pN0 cohort, the patterns of recurrence were different according to pT stage: locoregional recurrence was the most common in patients with pT1-2 disease (57.1%), distant was the most common in patients with pT3 disease (57.1%), and peritoneal was the most common in patients with pT4a disease (66.7%). For the pN+ cohort, distant metastasis was the most common pattern irrespective of pT stage. The site-specific trend of recurrence showed that locoregional recurrence increased within 5 years in patients with pN0-2 disease but plateaued 3 years after surgery in patients with pN3 disease. Time to recurrence was significantly longer for the pN0 cohort compared with the pN+ cohort (median:25 vs 16 months=0.001). Moreover, post-recurrence survival was significantly better for the pN0 cohort than for the pN+ cohort (median:12 vs 6 months<0.001), especially in patients with non-peritoneal recurrence, late recurrence, single recurrence, and receipt of potential curative treatment.

Conclusions

There was a significant difference in recurrence patterns survival between node-negative and node-positive patients. For node-negative patients, follow-up strategies should be considered according to pathologic T stage, while the key to follow-up for node-positive patients is distant metastasis.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

144P - Clinical implication of DNA damage response gene in patients with stage II or III gastric cancer (ID 707)

Presentation Number
144P
Lecture Time
09:00 - 09:00
Speakers
  • In Gyu Hwang (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study was conducted to evaluate the relation of DNA damage repair (DDR) to clinical outcomes in gastric cancer patients with stage II or III treated gastrectomy.

Methods

From January 2005 to December 2017, 217 patients with stage II or III gastric cancer were analyzed for disease free survival (DFS) and overall survival according to DDR gene status. Immunohistochemical assessment of MLH1, MSH2, ARID1A, PARP-1, BRCA1 and ATM was performed in biologic samples.

Results

Among the 217 patients, the most commonly mutated DDR gene was MSH2 (n = 208, 95.9%), followed by BRCA1 (n = 191, 88.0%), MLH1 (n = 184, 84.8%), ARID1A (n = 170, 78.3%), ATM (n = 146, 67.3%) and PARP-1 (n=120, 55.3%). The high expression levels of PARP-1 group had a significantly longer 5-year OS rate as compared to low expression level of PARP-1 group (62.7% vs. 48.1%, HR 0.649, 95% CI 0.433-0.974, P = 0.035). In the multivariate OS analysis, TNM stage (HR = 5.202, P < 0.001), high expression PARP-1 (HR = 0.583, P = 0.011) and adjuvant chemotherapy (HR = 0.382, P <0.001) were only significantly prognostic factor.

Conclusions

A subgroup of patients with gastric cancer may benefit from targeted therapy. High PARP-1 expression may be a good prognostic factor for gastric cancer particularly, stage II or III gastric cancer post-surgery.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

145P - A nomogram for predicting the benefit of adjuvant chemotherapy after resection in patients with Borrmann type IV gastric cancer (ID 709)

Presentation Number
145P
Lecture Time
09:00 - 09:00
Speakers
  • Qing-Zhu Qiu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

This study sought to explore prognostic factors for patients with Borrmann type IV gastric cancer and to establish a predictive model for survival benefit of postoperative adjuvant chemotherapy in such patients.

Methods

This study reviewed the clinical data of patients who underwent curative surgery at Fujian Medical University Union Hospital from 2006 to 2014 for Borrmann type IV gastric cancer using a prospective database. Cox regression analyses were performed to identify prognostic factors that formed the basis for a nomogram and risk groups. Establishment of risk groups to identify patients with Borrmann type IV gastric cancer who would benefit from adjuvant chemotherapy.

Results

265 patients who underwent R0 resection were included in this study.Multivariate analysis showed that BMI, tumour differentiation, pT stage, pN stage, and ASA score were independent prognostic factors. Patients in the ACT-group had longer OS than patients in the SA-group, although the p-value for this difference was marginally above the threshold for statistical significance (23.8% vs. 10.9%, p=0.057). Stratified analysis showed that there was no significant difference in OS between the ACT-group and the SA-group for each AJCC stage (stage II: 40.6% vs. 29.8%, p=0.44; stage III: 21.4% vs. 9.7%, p=0.056).A nomogram was established based on these independent risk factors, and nomogram scores were used to divide all patients into a high-risk group (score>16), an intermediate-risk group (8<score≤16) and a low-risk group (score≤8).Further stratified analysis based on AJCC stage showed that the 3-year survival rate was higher in the adjuvant chemotherapy group than in the surgery alone group for low- and intermediate-risk patients in each AJCC stage, while high-risk patients in stage III did not significantly differ.

Conclusions

The nomogram that we established may effectively be used to identify patients with Borrmann type IV gastric cancer who would benefit from postoperative adjuvant chemotherapy. Postoperative adjuvant chemotherapy can improve survival in low- and intermediate-risk patients.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

146P - Red cell distribution width and mean corpuscular volume ratio as a promising new marker for chemotherapy effects in remnant gastric cancer: An analysis of a multi-institutional database (ID 738)

Presentation Number
146P
Lecture Time
09:00 - 09:00
Speakers
  • Kai-Xiang Xu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To study the value of the ratio of the red blood cell distribution width (RDW) to the mean corpuscular volume (MCV) (RMR) in predicting the efficacy of adjuvant chemotherapy (AC) in residual gastric cancer (RGC).

Methods

A total of 379 patients who underwent resection for RGC at 7 hospitals in China from January 2004 to January 2016 were analyzed. A nomogram predicts survival was established to evaluate the effect of RMR through a decision curve.

Results

According to the RMR cut-off point (0.177), all patients were divided into Group L (RMR<0.177) (n = 179) and Group H (RMR ≥ 0.177) (n = 160). Patients with stage II and III disease with a high RMR who received AC had a significantly better 3-year OS than those who did not receive AC (P = 0.048 and 0.044), while AC had no significant effect on the survival of patients with low RMR. The independent prognostic factors for OS in patients with RGC who underwent AC were used to establish a nomogram. The C-index was 0.795, and the decision threshold was 0-85%. According to the nomogram, patients were divided into low-benefit patients with AC (point < 102 points) and high-benefit patients with AC (point ≥ 102 points).

Conclusions

The predictive model based on RMR in this study can provide a simple and accurate indication for postoperative AC in patients with RGC. It is recommended that postoperative AC be administered to high-benefit patients with a score of ≥102 on the nomogram.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

148P - MCV-the ideal answer to predict the prognosis of remnant gastric cancer: An analysis from a multi-institutional database (ID 746)

Presentation Number
148P
Lecture Time
09:00 - 09:00
Speakers
  • Kai Weng (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the mean hemoglobin volume (MCV) in predicting the prognosis of residual gastric cancer (RGC).

Methods

A total of 225 RGC patients who underwent R0 resection in three hospitals in China from January 2003 to June 2015 were enrolled. The 3-year survival time were compared. Two-step regression was performed to analyze the effect of MCV on prognosis in RGC patients.

Results

A total of 208 patients were included in the final analysis, including 135 in Group L (MCV < 100 fl) and 73 in Group N (100 ≤ MCV < 120 fl). In different hospitals, there were different RGC occurrence times and initial gastric surgery intervals and different initial surgical reconstruction methods, the MCV value was not significantly correlated with hemoglobin content (R2=0.397). Comparing the 3 years overall survival time (OS) and disease-free survival time (DFS) with Group L, Group N patients were all better (P < 0.001). The stratified analysis showed that for stage III, with no anemia or mild anemia and chemotherapy, Group N patients had significantly better OS and DFS than the Group L patients (P < 0.05). Two-step multivariate analysis showed that MCV was an independent factor for the OS and DFS, and both the OS and DFS decreased as the MCV decreased (P<0.001).

Conclusions

MCV showed significant heterogeneity in patients with different RGC. Patients with low MCV have a significantly poor prognosis, and the MCV can therefore be a simple and effective indicator for assessing the prognosis of patients with RGC.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

149P - Molecular and clinical characteristics of patients with resectable gastric cancer (ID 796)

Presentation Number
149P
Lecture Time
09:00 - 09:00
Speakers
  • Zhi Zheng (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) is one of the most common malignancies and a leading cause of cancer deaths worldwide. Currently, the genomic researches mainly focused on metastatic GC, but the clinico-molecular characteristics of resectable GC were poorly investigated.

Methods

A total of 47 resectable GC patients were enrolled. All kinds of genomic mutations were identified by next-generation sequencing (NGS) with Acornmed panel. Programmed death-ligand 1 (PD-L1) expression was analyzed by immunohistochemistry staining.

Results

Overall, a total of 582 mutations were identified from all the patients. TP53, LRP1B, ARID1A, and MDC1 were the most commonly mutated genes in resectable GC. Genomic data revealed significant mutual exclusivity between alterations in TP53 and PIK3CA (p < 0.05) and between those in TP53 and DICER1 (p < 0.05), as well as mutual co-occurence between alterations in FAT1 and ERBB3 (p < 0.05) and between those in FAT1 and NOTCH2 (p < 0.05). Additionally, ARID1A and APC alterations were significantly associated with poor differentiation (p < 0.05), and frequency of ARID1A mutations was markedly higher in intestinal-type GC than diffuse GC (p < 0.05). PD-L1 expression was analyzed in 45 tumors, and 33.3% of them showed positive PD-L1 expression. Further analysis demonstrated that KMT2D and ARID1A alterations were strikingly correlated with positive PD-L1 expression (p < 0.05). The median tumor mutational burden (TMB) in resectable GC was 6.38 mutations/Mb, and AR, CDH1, NOTCH2, and FAT1 mutations were remarkably associated with high TMB (p < 0.05). We further found that patients with positive PD-L1 expression tended to have low TMB (p = 0.057).

Conclusions

This study is of great significance in understanding the population characteristics of patients with resectable GC, which will be useful to guide personalized therapy and promote the clinical management in this population.

Legal entity responsible for the study

Zhi Zheng.

Funding

Beijing Municipal Science & Technology Commission.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

150P - Real-world assessment of the treatment patterns associated with unresectable advanced and metastatic gastric cancer in China (ID 778)

Presentation Number
150P
Lecture Time
09:00 - 09:00
Speakers
  • Xiao Sun (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) [including gastroesophageal junction cancer (GEJC)] has the second highest incidence and third highest mortality rate of all malignancies in China. For patients diagnosed with unresectable advanced or metastatic (UAM) GC, the prognosis and survival outcomes are extremely poor.

Methods

This was a retrospective real-world observational study using an oncology database operated by Digital China Health (DCH), which is comprehensive electronic health record (EHR) repository of patient demographics, clinical (including imaging, pathology.), medication use, healthcare resource use (HCRU) and cost data. Patients having ≥2 inpatient records with a primary ICD-10 code of GC were selected from Jan 1st, 2012 through Dec 31st, 2018. The first date of inpatient admission was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified as resectable vs. unresectable advanced or metastatic (UAM). Demographics, clinical parameters, medication utilization, HCRU, and costs incurred were tracked for these cohorts.

Results

A total of 7,464 patients met the inclusion/exclusion criteria, of whom 14.1% (n=1056) had UAM GC. The mean age at index date of patients with UAM GC was 57.7 (SD=11.3) years, with the vast majority male (70.5%). 69.3% (n=732) of patients with UAM GC received first line (1L) chemotherapy, the most frequent being S-1 + oxaliplatin (SOX, 22.7%) fluorouracil + oxaliplatin (FOLFOX, 12.6%) and capecitabine + oxaliplatin (XELOX, 11.2%). The average duration of 1L chemotherapy was 133.8 ± 115.9 days. Of these 1L line patients, 29.5% (n=216) went on to 2L treatment and 25.9 % (n=56) of 2L patients received 3L treatment. The main disease complications due to UAM GC were gastro-intestinal obstructions (7.8%) and ascites (7.5%). The main adverse drug events due to treatment were anemia (45.6%) and liver impairment (41.1%).

Conclusions

The majority of patients with UAM GC received 1L treatment. The top three regimens were SOX, FOLFOX and XELOX which seems consistent with Chinese Society of Clinical Oncology (CSCO) GC treatment guidelines.

Legal entity responsible for the study

Bristol-Myers Squibb Pharmaceutical Corp.

Funding

Bristol-Myers Squibb Pharmaceutical Corp.

Disclosure

X. Sun, Y. Qu: Research grant/Funding (self): Bristol-Myers Squibb. P. Navaratnam, H.S. Friedman: Research grant/Funding (self): Bristol-Myers Squibb. J. Gricar, H. Xiao: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb.

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e-Poster Display Session (ID 87) Poster Display

151P - Treatment patterns, healthcare resource use, economic and survival outcomes associated with unresectable advanced metastatic gastric cancers in Taiwan (ID 902)

Presentation Number
151P
Lecture Time
09:00 - 09:00
Speakers
  • Chee Jen Chang (Taoyuan City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths in Taiwan. Even with significant strides that have been made in GC early detection and management in Taiwan in recent years, patients with GC (including gastro-esophageal junction cancer, GEJC) that present with unresectable advanced metastatic disease (UAM) remain at risk for poor survival outcomes.

Methods

This was a retrospective ‘real world’ observational study using the linked Taiwan National Health Insurance Research Database, which contains health claims data on almost the entire Taiwan population, and the Taiwan National Cancer Registry. Patients having at least one hospital record with a primary ICD-9 or ICD-10 code of GC/GEJC were selected from Jan 1st, 2013 through Dec 31st, 2018. The first date of GC/GEJC diagnosis was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified by staging, clinical presentation [i.e. resectable vs. unresectable advanced metastatic (UAM)]. Key characteristics such as demographics, clinical parameters, medication utilization, health care resource utilization, costs incurred, and survival were tracked for the overall population and both cohorts.

Results

A total of 3736 UAM GC patients were identified with a mean age of 68.0 (sd=15.2) years, with most patients being male (n=2248, 60.2%). The majority of UAM GC patients were Stage 4 (n=2270, 60.8%) and most patients were identified as having adenocarcinoma (n=2847, 76.2%). Nearly half the patients received 1st line (1L) therapy (n=1846, 49.4%) with the most common 1L therapies being Capecitabine + Oxaliplatin (n=604, 32.7% of 1L), S-1 (n=280, 15.2% of 1L) and Capecitabine monotherapy (n=209, 11.3% of 1L). Only 38.2% (n=1428) of patients survived 1 year with the annualized post-index GC-related costs being New Taiwan (NT) $ 396,590 (sd = NT$ 412,523).

Conclusions

The most common 1L chemotherapeutic treatments for UAM GC patients were Capecitabine + Oxaliplatin, S-1 and Capecitabine. In Taiwan, UAM GC patients appear to have poor survival and incur high GC-related costs, which suggests the need for new treatment options.

Legal entity responsible for the study

Bristol-Myers Squibb Pharmaceuticals Corp.

Funding

Bristol-Myers Squibb Pharmaceuticals Corp.

Disclosure

C.J. Chang, Y. Tsai, H.S. Friedman, P. Navaratnam: Research grant/Funding (self): Bristol-Myers Squibb. J. Gricar, H. Xiao: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb.

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e-Poster Display Session (ID 87) Poster Display

153P - Mutational landscape of gastric cancer (GC) in adolescents and young adults (AYA) in Asia from 2015-2019 (ID 929)

Presentation Number
153P
Lecture Time
09:00 - 09:00
Speakers
  • Evelyn Yi Ting Wong (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gastric cancer (GC) is an aggressive cancer and it is thought that they have a worse prognosis in AYA due to delayed diagnosis and a more aggressive tumour biology. There is an increasing trend to adopt next-generation sequence (NGS) to identify tumour genomic alterations for precision medicine in AYA. We aim to study the differences in the mutational landscape of GC in AYA and how it correlates to outcomes in a single-centre high-volume Asian institution.

Methods

Patients diagnosed between 16-39 years old with GC between 2015 to 2019 in our centre, National Cancer Centre Singapore, were included in this study.

Results

A total of 50 AYA GC patients were referred to NCCS between 1st January 2015 and 31st December 2019. 7 patients were excluded from this analysis (3 due to incomplete data and 4 were neuroendocrine tumours). The median age (n=43) was 35(22-39) with 22 males (51.2%) and majority (53.5%, n=23) having signet ring cell carcinoma. 28 patients (65.1%) had metastatic disease at diagnosis. Out of the 43 patients, only 60.5%(n=26) and 58.1%(n=25) were tested for programmed death-ligand 1(PD-L1) and DNA mismatch repair (MMR) respectively. 1 patient (3.8%) had MLH 1 loss and 1 patient (4.5%) had PD-L1 percentage of more than 50% by using combined positive score (CPS). 32 patients (74.4%) had the human epidermal growth factor receptor 2(HER2) tested, of which 5 were HER2 positive (15.6%). With a median follow-up of 11 months, median OS was 16.0 months (range 0.5- 111.3 months). There was no significant differences between subgroups with regards to age(p=0.931), presence of signet-ring histology (p=0.135), histology grade (p=0.384) and HER2 positivity (p=0.66).

Conclusions

Gastric cancer in the young behaves differently and generally seem more aggressive in the young regardless of gender. Further studies to evaluate how the differences in the mutational landscape of gastric cancer in the adolescents and young adults impact prognosis and treatment paradigm.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

154P - A multicenter, prospective study of apatinib plus chemotherapy as neoadjuvant treatment for locally advanced gastric cancer (ID 486)

Presentation Number
154P
Lecture Time
09:00 - 09:00
Speakers
  • Yi-Hui Tang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Apatinib, a novel treatment option for chemotherapy-refractory advanced gastric cancer (AGC), has not yet been evaluated in patients with locally AGC. This trial investigated the efficacy and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally AGC.

Methods

Patients with M0 and either T2-T4 or N+ disease received apatinib (500 mg orally once daily on days 1-21 and discontinued in the last cycle) plus SOX (S-1, 40-60 mg orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1) given every 3 weeks for 2-5 cycles. D2 gastrectomy was performed 2-4 weeks after the last cycle. To further compare the efficacy and safety between apatinib plus SOX (ASOX group) and SOX alone (SOX group), we reviewed historical control patients receiving SOX as neoadjuvant chemotherapy at the central center. The primary end point was the R0 resection rate.

Results

Between July 2017 and June 2019, 48 and 58 patients were enrolled in the ASOX and SOX groups, respectively. Forty patients in the ASOX group (83.3%) and 47 patients in the SOX group (81.0%) underwent surgery, with R0 resection rates of 75.0% and 67.2%, respectively (P=0.382). The proportion of patients with T downstaging in the ASOX group was significantly higher than that in the SOX group (36.4% vs 18.5%, P=0.036). For patients with target lesions, the radiological response rate was significantly higher in the ASOX group (75.0% vs 38.5%, P=0.015). Moreover, the ASOX group was associated with significantly higher proportions of patients achieving major pathological response (25.0% vs 10.3%, P=0.046). Grade 3 toxicities occurred in 33.3% of the ASOX patients, and no grade 4 toxicities or drug-related deaths were observed.

Conclusions

Apatinib combined with SOX showed promising efficacy with an acceptable safety profile as the first-line neoadjuvant treatment for locally AGC.

Clinical trial identification

NCT03192735.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

155P - Surgical outcomes and technical performance of robotic versus laparoscopic total gastrectomy for gastric cancer: A prospective comparative study FUGES-014 (ID 720)

Presentation Number
155P
Lecture Time
09:00 - 09:00
Speakers
  • Hua-Gen Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Despite the increasing application of robotic surgery in patients with gastric cancer, however, for the complex minimally invasive total gastrectomy, no reports are supporting robotic surgery that can improve surgical performance and clinical outcomes.

Methods

In this prospective study, 50 patients were assigned to underwent robotic total gastrectomy (RTG) between March 2018 to February 2020 at a tertiary referral teaching hospital. Patients who underwent laparoscopic total gastrectomy (LTG) in the FUGES-002 study were matched to compare the surgical outcome and surgery task load of RTG and LTG. Objective structured assessment of technical skill (OSATS) was used to evaluate the technical performance.

Results

After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The total operative time in the RTG group was longer than that in LTG Group (217.1 minutes vs. 186.1 minutes, P < 0.001). Compared with LTG, the RTG group had less intraoperative blood loss (66.4 ml vs. 38.7 ml, P = 0.042). The average number of errors in the RTG group was 43.2 times/case, which was less than 53.8 times/case in the LTG Group (P < 0.001). Compared with LTG, RTG had a higher OSATS score (30.2 vs. 28.4, P < 0.001). RTG is superior to LTG in terms of respect for tissue, time and motion, instrument handling, and knowledge of specific procedures. The mean number of lymph nodes (LNs) retrieved in the RTG group and LTG group was 47.9 and 44.0, respectively. Significantly more extraperigastric LNs were retrieved in the RTG group than in the LTG group (20.2 vs. 17.5, P = 0.039). RTG group had a lower Surg-TLX score than LTG Group (33.2 vs. 39.8, P < 0.001). The postoperative recovery processes in the RTG group were shorter than those in the LTG Group. No significant difference was found between the RG and LG groups in the incidence (14.6% vs 16.7%, P = .86) or severity of complications.

Conclusions

In the complex radical gastrectomy, compared with traditional laparoscopic surgery, the use of the robotic system provides a technically superior operative environment and lower surgeon workload for minimally invasive surgery.

Clinical trial identification

NCT03524287.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

156P - Safety and feasibility of laparoscopic spleen-preserving splenic hilar lymphadenectomy during total gastrectomy for advanced proximal gastric cancer: A randomized clinical trial (ID 477)

Presentation Number
156P
Lecture Time
09:00 - 09:00
Speakers
  • Jian-Xian Lin (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The splenic hilar lymph node (No. 10 LN) dissection is still controversial for patients with advanced proximal gastric cancer (APGC) not invading the greater curvature. We aim to evaluate the short-term outcomes of laparoscopic spleen-preserving No. 10 lymphadenectomy (LSPL) for APGC not invading the greater curvature and the characteristic of No. 10 LN metastasis.

Methods

Between January 2015 and December 2018, 536 APGC patients with clinical stage cT2-4a/N0-3/M0 not invading the greater curvature were enrolled and randomized to receive laparoscopy-assisted total gastrectomy with either D2 lymphadenectomy (D2 group) or D2 lymphadenectomy without No. 10 LN dissection (D2- group). The morbidity and mortality within 30 days after surgery, and number of retrieved LNs between the two groups were compared. Risk factors and the metastasis rate of No.10 LN were analyzed.

Results

The present analysis included 263 patients in each group. There were no significant differences in the intraoperative and postoperative morbidity between the D2 and D2- groups (all P>0.05), and no mortality in both groups. There were more retrieved LNs in the D2 group than in the D2- group (45.1 vs 40.6, P=0.001). The metastasis rate of the No. 10 LN was 13.3% (35/263): 4.9% (2/41) in the early stage, and 14.9% (18/223) in the advanced stage. Pathological T (pT) stage and pN stage were related to No. 10 LN metastasis. The metastasis rates of No. 10 LN in T3-4a tumors located in the lesser curvature, posterior wall or multiple parts were all higher than 10%.

Conclusions

Experienced surgeons can safely perform LSPL for APGC with more retrieved LNs. For APGC located in the lesser curvature, posterior wall, or multiple parts with a clinical stage cT3-4a, the dissection of No.10 LN is recommended, but long-term follow-up is still required.

Clinical trial identification

NCT02333721.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

157P - Efficacy and safety of penpulimab (AK105), a new generation anti-programmed cell death-1 (PD-1) antibody, in upper gastrointestinal cancers (ID 687)

Presentation Number
157P
Lecture Time
09:00 - 09:00
Speakers
  • Amy Prawira (Sydney, Ontario, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Upper gastrointestinal (UGI) cancers are a group of highly aggressive malignancies with poor prognoses. Immunotherapy is emerging as an effective treatment option for some of these cancers. Penpulimab, a new generation anti-PD-1 monoclonal antibody, was engineered to optimize receptor occupancy by improving duration of drug binding, and to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function. Here, we present the preliminary antitumor and safety data on Penpulimab in patients (pts) with advanced UGI malignancies.

Methods

Pts with advanced cancers, relapsed or refractory to standard therapy but naïve to immune checkpoint inhibitors (ICIs), were enrolled in two phase I trials of Penpulimab (NCT03352531 and NCT04172506). Pts received Penpulimab IV at 1-10 mg/kg Q2W or 200mg Q2W until disease progression or unacceptable toxicity. Antitumor activity was investigator-assessed per RECIST v1.1 criteria.

Results

As of 1st July 2020, 67 pts with UGI cancers received Penpulimab for a median of 6 (1–64) doses. The antitumor activity of Penpulimab in the 60 pts evaluable for efficacy is shown below. 11/13 (85%) responders had ongoing responses at data cutoff date.

Pancreatic cancer (PCA), n=9 Cholangiocarcinoma (CCA), n=9 Gastric/ gastroesophageal junction (GEJ) cancer, n=19 Hepatocellular carcinoma, (HCC), n=23
ORR, % (95% CI) 11.1 [0.3, 48.2] 22.2 [2.8, 60.0] 26.3 [9.1, 51.2] 21.7 [7.5, 43.7]
DCR, % (95% CI) 33.3 [7.5, 70.1] 44.4 [13.7, 78.8] 42.1 [20.3, 66.5] 52.2 [30.6, 73.2]
Median DoR, months (range) 22.1+ 21.1 [0.03+, 21.1] NR [3.7+, 14.8+] NR [3.7+, 23.0+]
.

Treatment-related adverse events (TRAEs) occurred in 44.8% of pts. There were no discontinuations due to drug-related AEs or drug-related deaths. Grade ≥3 TRAEs occurred in 5 pts (7.5%) – raised liver enzymes (n=2), adrenal insufficiency (n=1) and hyponatraemia (n=1) in the same pt, intestinal obstruction (n=1), and hypertension (n=1).

Conclusions

Penpulimab was well tolerated and demonstrated encouraging antitumor activity with durable response in pts with advanced UGI cancers, including PCA and CCA, which are generally resistant to single agent ICI. Penpulimab in combination with anlotinib, a multi-targeted receptor tyrosine kinase inhibitor, is being evaluated in phase III studies for 1L HCC (NCT04344158) and 2L Gastric/GEJ (NCT04385550).

Clinical trial identification

NCT03352531; NCT04172506.

Legal entity responsible for the study

Akeso Biopharma Inc.

Funding

Akeso Biopharma Inc.

Disclosure

A.R.A. Mislang: Honoraria (self): BMS. A. Cooper: Honoraria (self): MSD; Travel/Accommodation/Expenses: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Roche. X. Jin, K.Y. Kwek: Shareholder/Stockholder/Stock options, Full/Part-time employment: Akeso Biopharma. B. Li, M. Wang, D. Xia: Y. Xia: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Akeso Biopharma. A. Prawira: Research grant/Funding (institution), Non-remunerated activity/ies: Akeso Biopharma; Research grant/Funding (institution), Non-remunerated activity/ies: Beigene; Research grant/Funding (institution), Non-remunerated activity/ies: Corvus; Research grant/Funding (institution), Non-remunerated activity/ies: CStone; Research grant/Funding (institution), Non-remunerated activity/ies: Macrogenics; Research grant/Funding (institution), Non-remunerated activity/ies: Five Prime; Research grant/Funding (institution), Non-remunerated activity/ies: Virogin; Research grant/Funding (institution), Non-remunerated activity/ies: QBiotics; Research grant/Funding (institution): Arcusbio; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): ENB Therapeutics; Research grant/Funding (institution): Henlius; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): INXMed; Research grant/Funding (institution): Merck/MSD; Research grant/Funding (institution): Janssen. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

158P - A phase II study of trastuzumab with S-1 plus oxaliplatin for HER2-positive advanced gastric cancer (HIGHSOX study): Final report (ID 275)

Presentation Number
158P
Lecture Time
09:00 - 09:00
Speakers
  • Atsuo Takashima (Tokyo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

We previously reported that trastuzumab (Tmab) combined with S-1 plus oxaliplatin (SOX) exhibited promising activity with well-tolerated toxicities in patients (pts) with human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) (Gastric Cancer 2019). Here, we report the results of a follow-up extension, including exploratory analyses performed to investigate predictive factors for treatment effects.

Methods

We conducted an open-label, phase II trial in pts with chemo-naïve, HER2-positive AGC. Pts received S-1 (40 mg/m2) BID orally on days 1–14, oxaliplatin (130 mg/m2) intravenously on day 1, and Tmab (course 1, 8 mg/kg; course 2, 6 mg/kg) intravenously on day 1 of a 21-day cycle. The primary endpoint was objective response rate (ORR); secondary end points included overall survival (OS), progression-free survival (PFS), and adverse events. A sample of 75 provided the study with 90% power to test a hypothesis of threshold RR of 50% and an expected RR of 65% at a one-sided significance level of 0.05 using the binomial test.

Results

Seventy-five patients were enrolled from June 2015 to January 2018. Pts characteristics were previously reported. In the full analysis set of 75 pts with a median follow up of 20.6 months, ORR was 70.7% (95% confidence interval (CI): 59.0–80.6) and the disease control rate was 93.3% (95% CI: 85.1–97.8). OS and PFS (median) were 20.6 (95% CI: 15.9–29.2) and 8.8 (95% CI: 7.3–11.8) months, respectively. In the exploratory analyses, both OS and PFS were longer in pts with HER2 3+ (n=55) than in pts with 2+ (n=20) [OS, 25.9 vs.16.3 months; hazard ratio (HR), 0.59; 95% CI: 0.329–1.053; P=0.07; PFS, 9.8 vs. 7.0 months; HR, 0.72; 95% CI: 0.421–1.229; P=0.23]. Pts who underwent conversion surgery (n=8) exhibited dramatically prolonged survival [OS, not reached; 3-year survival rate, 85.7% (95% CI: 33.4–97.9), PFS, 34.5 months (95% CI: 6.9–not reached)].

Conclusions

Tmab in combination with SOX exhibited promising therapeutic effects in pts with HER2-positive AGC. Efficacy was enhanced in pts with HER2 3+ and in those who underwent conversion surgery.

Clinical trial identification

UMIN000017602.

Legal entity responsible for the study

The authors.

Funding

Japanese Foundation for Multidisciplinary Treatment of Cancer.

Disclosure

A. Takashima: Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self), Research grant/Funding (self): Takeda; Honoraria (self): Eli Lilly; Honoraria (self): Ono; Honoraria (self): Yakult; Honoraria (self): Chugai; Research grant/Funding (self): Sumitomo Dainippon; Research grant/Funding (institution): LSK BioPartners. K. Minashi: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Ono. S. Kadowaki: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Ono; Research grant/Funding (institution): BMS; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Bayer; Honoraria (self): Merck. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Daiichi Sankyo; Honoraria (self): Dainippon Sumitomo; Honoraria (self): Boehringer Ingelheim; Honoraria (self): MSD. K. Amagai: Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution): MSD; Honoraria (self): Eli Lilly; Honoraria (self): BMS; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Daiichi Sankyo; Honoraria (self): Hisamitsu. N. Machida: Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self): Eli Lilly ; Honoraria (self): Ono; Honoraria (self): BMS; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Nippon Kayaku; Honoraria (self): Daiichi Sankyo; Honoraria (self): MSD. M. Goto: Honoraria (self): Taiho; Honoraria (self): Yakult; Honoraria (self): Chugai; Honoraria (self): Ono; Honoraria (self): Takeda; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Novartis; Honoraria (self): Bayer; Honoraria (self): Mochida. N. Ishizuka: Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self): MSD. D. Takahari: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self): Eli Lilly; Honoraria (self): BMS. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

159P - Open surgery can improve the 3-year postoperative survival in some patients with advanced gastric cancer compared with laparoscopic surgery: A multicenter, propensity score matching, in-depth analysis (ID 702)

Presentation Number
159P
Lecture Time
09:00 - 09:00
Speakers
  • Ze-Ning Huang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The impact of time on the efficacy of advanced distal gastric cancer (ADGC) remains unclear. At 3 years postoperatively, the efficacy of oncologic surgery for ADGC needs to be confirmed.

Methods

A total of 1256 patients with ADGC at two teaching institutions in China from April 2007 to December 2014 were enrolled. The general data of the two groups were matched using propensity scores. Restricted mean survival time (RMST) was used to compare survival.

Results

After matching, 461 patients each in the open distal gastrectomy (ODG) and laparoscopic distal gastrectomy (LDG) groups were analyzed. The 3- and 5-year overall survival (OS) and disease-free survival in ODG group were comparable to those in LDG group. RMST-stratified analysis showed that the 3-year RMST of ODG group was similar to that of LDG group (-1.38 years, P=0.163) in cT4a patients, whereas the 5-year RMST had significant differences between groups (-8.36 years, P=0.005). In further stratified analysis, when patients with cT4a and tumor was >5 cm, the 3-year RMST of ODG group was similar to that of LDG group (0.98 year, P=0.480); however, the 5-year RMST was significantly longer in ODG group (4.67 years, P=0.042). Multivariate regression analysis showed that ODG is a protective factor for 5-year OS in patients with cT4a and tumors >5 cm.

Conclusions

Beyond 3 years, ODG can improve the survival of patients with serous infiltration and tumors >5 cm by reducing the risk of recurrence. The present findings can serve as a reference for the preoperative selection of GC surgery options and the setting of follow-up time for clinical studies.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

160P - Phase II study of sintilimab combined with FLOT regimen for neoadjuvant treatment of gastric or gastroesophageal junction (GEJ) adenocarcinoma (ID 879)

Presentation Number
160P
Lecture Time
09:00 - 09:00
Speakers
  • Ning Li (Zhengzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Although FLOT has been recognized as the first choice for neoadjuvant chemotherapy in gastric or GEJ adenocarcinoma, its efficacy needs to be improved. Sintilimab, a fully human IgG4 monoclonal antibody that binds to programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. We aimed to assess the activity and safety profile of the combination of FLOT and sintilimab for neoadjuvant treatment of gastric or GEJ adenocarcinoma.

Methods

In this ongoing, single-arm, phase II study, we recruited patients from Henan Cancer Hospital in China with histopathologically diagnosed resectable gastric or GEJ adenocarcinoma who had clinical T3/N+ or higher stage. Patients were given 4 cycles of FLOT (docetaxel 50 mg/m2, oxaliplatin 80 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2, 24-h infusion on day 1, q2w) in combination with 3 cycles of sintilimab (200mg, iv, d1, q3w), followed by surgery and 4 postoperative cycles of FLOT. The primary endpoint was pathological complete response (pCR). The secondary endpoints included major pathological remission (MPR) and objective response rate (ORR).

Results

Between Aug 10, 2019, and Jul 15, 2020, 19 patients were enrolled and commenced treatment. The grade 3 or 4 treatment-related adverse events (TRAE) included diarrhea (10.5%), leukopenia (5.3%), neutropenia (5.3%), anaemia (10.5%). Most frequent grade 1 or 2 TRAE were leukopenia (42.1%), neutropenia (31.6%) and Glutamic-pyruvate transaminase increased (42.1%). A total of 17 patients (89.4%) were eligible for efficacy assessment, and among 9 patients who experienced D2 resection, 6 (66.7%) achieved MPR, including 2 (22.2%) with pCR. According to RECIST v1.1, 6 of 17 patients (35.3%) achieved partial response (PR), and 11 of 17 patients (64.7%) achieved stable disease (SD). The ORR and disease control rate (DCR) for 17 patients were 35.3% and 100%, respectively.

Conclusions

Neoadjuvant combination of sintilimab and FOLT is a safe and efficacious treatment option for patients with gastric or GEJ adenocarcinoma, and 22.2% pCR rate is encouraging. Our clinical study (NCT04341857) is still enrolling, and the survival effects are under follow up.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

161P - Adjuvant tegafur/gimeracil/oteracil (S-1) versus platinum-based chemotherapies for resectable gastric cancer: Real-world experience and a propensity score matching analysis (ID 368)

Presentation Number
161P
Lecture Time
09:00 - 09:00
Speakers
  • Chih Chieh Yen (Tainan City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Postoperative adjuvant chemotherapy has changed the clinical paradigm in resectable gastric cancer. S-1 is an orally available chemotherapeutic with promising efficacy in Asia. However, the real-world experience of adjuvant S-1 in patients with resectable gastric cancer is seldom reported. A comparison with other platinum-based chemotherapies also warrants further investigation.

Methods

We retrospectively evaluated patients with resectable stage I to III gastric cancer who received S-1 (S-1, n=52), platinum-based chemotherapies (Platinum, n=85) and operation alone (OP, n=128) from Jan 2013 to Oct 2018. Recurrence-free (RFS) and overall survivals (OS) were compared with a propensity score matching analysis. Adverse effects, dosage and predictive factors for S-1 were also described.

Results

Group OP and S-1 had more patients with early stages of the disease as compared with Others. In a median follow-up of 39.4 months, Group S-1 had a trend of longer RFS and OS as compared with Platinum but it did not reach statistical significance (5-year RFS/OS rates: S-1 vs. Platinum, 49.5/58.3% vs. 40.2/50.6%, HR=0.85/0.70, p=0.575/0.330). Group S-1 with N3 disease had significantly longer RFS (S-1 vs. Platinum, undefined vs. 17.3 months, HR=0.33, p=0.046) but the OS difference was insignificant. S-1 was well-tolerated while platinum-doublets were associated with more severe adverse effects. The relative dose intensity of S-1 was 71.8%. In the subgroup analyses, patients with N3 disease, diffuse type tumors and Helicobacter pylori infection were potentially favorable in RFS when treated with adjuvant S-1. Early disease stages, N0 disease and low CEA were independent predictors for the selection of S-1.

Conclusions

Patients with resectable gastric cancer who received adjuvant S-1 had a comparable survival but better tolerability as compared with platinum-based regimens. Patients with diffuse type tumor, Helicobacter pylori infection and N3 disease derived additional benefits from S-1. The real-world experience revealed that S-1 was relatively under-dosed and selected according to disease stage, lymph node involvement and CEA level.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

162P - Evaluation of neutrophil/lymphocyte ratio (NLR) in monitoring anastomotic leakage after radical total gastrectomy for gastric cancer (ID 485)

Presentation Number
162P
Lecture Time
09:00 - 09:00
Speakers
  • Ru-Hong Tu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

It was unclear whether neutrophil/lymphocyte ratio (NLR) in gastric cancer patients are related to anastomotic leakage (AL). We aimed to evaluate the monitoring value of NLR for AL after radical gastrectomy for gastric cancer.

Methods

Two thousand eight hundred and fifty-five patients receiving radical total gastrectomy with Roux-en-Y esophagojejunal anastomosis for gastric cancer were included, and the cumulative sum (CUSUM) curve was used to dynamically monitor NLR changes.

Results

The incidence of AL was 2.6% (75/2855). The median diagnosis time for AL was 7 (2-17) days, and the median healing time was 19 (5-98) days. According to the CUSUM exceeded the limit value (3σ: 3 standard deviations) or not, the patients were divided into ≥3σ group and <3σ group. The 5 dead patients were in the ≥3σ group, and the median healing time of the other patients was 32 (7-98) days, which was longer than that of patients in the <3σ group [11 (5-28) days, p<0.001]. And 43.5% of patients in the ≥3σ group had severe complications (Clavien-Dindo grade ≥3), which were higher than those in the <3σ group (17.2%, p=0.019). Baseline NLR <2.5, AL occurred <7 days, and CUSUM change ≥3σ were independent risk factors affecting delayed healing (>19 days) or death. The area under curve (AUC) of receiver operating characteristic (ROC) of the scoring system was 0.913. The healing rate of patients in low, medium and high-risk group ≤19 days was 95.7%, 47.4% and 6.1%, respectively.

Conclusions

NLR can dynamically monitor the healing process of AL. The scoring system constructed based on NLR can effectively identify high-risk populations with delayed AL healing or death, providing an objective basis to develop a reasonable treatment plan.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

163P - Gastrointestinal stromal tumours (GIST) in adolescents and young adults (AYA) in an Asian institution from 2002 to 2018 (ID 931)

Presentation Number
163P
Lecture Time
09:00 - 09:00
Speakers
  • Evelyn Yi Ting Wong (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

GIST is not common in AYA patients and the data on AYA GISTs are limited. In our institution, the typical adult GIST patient is male (52.9%), with mutations in KIT (53.6%) or PDGFR (4.2%), has gastric as the primary location (54.4%), and a five-year overall survival (OS) of 51%. We studied the clinical and genetic characteristics and prognoses of AYA GISTs.

Methods

All GIST patients diagnosed between the ages of 16-39 at National Cancer Centre Singapore from 1 January 2002 to 31 December 2018 were included. We retrospectively studied their clinico-molecular characteristics and outcomes.

Results

41 AYA GIST patients were seen with a median age of 34 years old. 25 patients (61.0%) were male. 27 patients (65.9%) were Chinese. 9 (22.0%) had metastatic disease at diagnosis. The tumours were primarily in the jejunum/ileum (41.5%, n=17) or stomach (34.1%, n=14). 25 patients (61.0%) had tumor mutation testing performed. Of these, 19 (76%) had KIT and one (4%) had PDFGRA. 5 (20%) were KIT/PDGFR wildtype. Of those with KIT mutations, 17 (89.5%) were in exon 11, while 2 (10.5%) were in exon 9. The PDGFRA mutation was in exon 18. No data is available on genetic syndromes. 24 patients (58.4%) received curative-intent treatment with 3 (12.5%) subsequently had local recurrences. 14 (58.3%) received imatinib in a neoadjuvant/adjuvant setting. 17 patients (41.5%) received palliative-intent treatment with 13 (76.4%) receiving palliative imatinib. 9 (52.9%) had Sunitinib after progression. The median follow-up was 48 months (0-165). 6 patients (14.6%) had demised. Median OS for all patients was 162.0 months (95% CI: 80.8– 243.2) with no significant differences with regards to age (p=0.07), gender (p=0.91), presence of a sensitising mutation (KIT Exon 9 and 11) (p=0.26), and treatment intent (p=0.2). A significant OS difference was found between patients undergoing curative or palliative intent (162.0 vs 65.0 months, p=0.001) and in patients with different primary tumor location (p=0.029). Out of the 6 patients with uncommon primary tumor locations, 3 had demised.

Conclusions

AYA GISTs differ from adult GIST. In our series, 61.0% had tumor mutation analysis performed. AYA GIST also has a higher rate of small intestine primary. Further studies are needed to evaluate the low mutation and genetic testing and clinico-molecular differences to better understand how these affect outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

164P - The impact of sarcopenia on chemotherapy toxicity and survival rate among hepatocellular carcinoma patients who underwent chemotherapy: A systematic review and meta-analysis (ID 231)

Presentation Number
164P
Lecture Time
09:00 - 09:00
Speakers
  • Elizabeth Marcella (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Sarcopenia is the loss of skeletal muscle mass and function that occurs with advancing age and certain diseases. It is a complication and independent risk factor for chemotherapy toxicity and mortality in patients with liver cirrhosis and hepatocellular carcinoma. The aim of this study was to study the impact of sarcopenia on chemotherapy toxicity and survival among hepatocellular carcinoma patients who underwent chemotherapy.

Methods

A systematic review was performed according to PRISMA guidelines. A literature search was conducted by two independent reviewers on all studies that included sarcopenia in hepatocellular carcinoma patients who underwent chemotherapy using PubMed, PubMed central, and Google Scholar databases. Study included elderly population was excluded. Outcome of interest included chemotherapy toxicity and overall survival. Data synthesis and statistical analysis were carried out using Review Manager software.

Results

A total of 10 studies were eligible for meta-analysis including a total of 1203 hepatocellular carcinoma patients. All included studies were retrospective cohort. Meta-analysis revealed a significant association between sarcopenia and overall survival (HR 1.76; 95% CI 1.37 – 2.25; P < 0.001). Sarcopenia was also associated with incidence of chemotherapy toxicity (OR 2.84; 95% CI 1.35 – 5.96; P = 0.006), including hand-foot syndrome, diarrhea, hepatic encephalopathy and hypertension. The quality of study assessed with Newcastle Ottawa Scale (NOS) showed “poor” in only 2 included studies while the remaining 8 studies were graded as “good”.

Conclusions

Sarcopenia can give negative impact on chemotherapy toxicities and survival outcomes for hepatocellular carcinoma patients who underwent chemotherapy. Prospective studies with a uniform definition of sarcopenia and same chemotherapy regimen are still needed.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

165P - Prognostic factors in sorafenib-treated hepatocellular carcinoma: Multicentre analysis of a European population sample (ID 999)

Presentation Number
165P
Lecture Time
09:00 - 09:00
Speakers
  • João Gramaça (Barreiro, Portugal)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Sorafenib has been the standard-of-care in advanced hepatocellular carcinoma (HCC). Prognostic factors such as BCLC stage and macroscopic vascular invasion (MVI), together with predictive factors of response such as neutrophil-lymphocyte ratio (NLR), cirrhosis etiology and extrahepatic spread (EHS) were found to be associated to survival outcomes. Nevertheless, these factors need to be fully validated. We intend to explore and identify prognostic factors for overall survival (OS) in a European population sample treated with sorafenib.

Methods

Multicentre retrospective evaluation of patients’ (pts) charts of HCC pts with ECOG performance status (PS) ≤2 treated with sorafenib between 2008 and 2019 in two Portuguese centres. Alfa- fetoprotein (AFP) < 200 ng/mL, EHS, Model for End-Stage Liver Disease-Na (MELD-Na) < 17, cutaneous toxicity, NLR < 2.3, MVI and previous locoregional treatment (LRT) were considered for stratification. Each factor was analyzed by Kaplan-Meier method for OS estimation and a multivariate Cox regression was performed.

Results

Eighty-six pts were analyzed, 15% female and with a median age (med) of 65.5 years [36-83]. Considering underlying cause, 45% pts had alcohol-related liver disease, 23% hepatitis C virus, 14% hepatitis B virus and 5% non-alcoholic steatosis hepatitis. Median OS was 8.5 months (m). Kaplan-Meier analysis of OS proved to be statistical significant in the following factors: AFP < 200 ng/mL med OS 12.5 m and ≥ 200 ng/mL 5.4 m (p < 0.0001); MELD-Na < 17 med OS 10.4 m and ≥ 17 4.8 m (p=0.015); absence of EHS med OS 10.0 m and presence of EHS med OS 7.3 m (p=0.028); previous LRT med OS 11.2 m and no LRT med OS 6.6 m (p=0.005). Multivariate Cox analysis identified extra-hepatic involvement (HR 1.002, p=0.041) and no previous LRT (HR 1.871, p=0.009) as risk factors.

Conclusions

HCC pts represent a heterogeneous population with many factors that potentially affect prognosis, such as geographic etiology difference in hepatic cirrhosis. In our sample, analysis of single-variable subgroups estimated greater OS in pts with AFP < 200 ng/mL, MELD-Na < 17, absence of EHS and previous LRT. The multivariate regression showed EHS and no previous LRT are independent factors for worse prognosis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

166P - Differences and similarities in presentation and management patterns in patients with hepatocellular carcinoma (HCC) across Hong Kong, Singapore and Thailand (ID 1035)

Presentation Number
166P
Lecture Time
09:00 - 09:00
Speakers
  • Pierce K. Chow (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

An estimated 841,000 new Hepatocellular Carcinoma (HCC) cases have been identified globally, with Asia having the highest incidence (73%). However, there is limited real world data on how HCC is diagnosed and on the preferred treatment modalities. This study aims to evaluate and compare the presentation and management patterns in patients with HCC across Hong Kong (HK), Singapore (SG) and Thailand (TH).

Methods

Primary research was conducted amongst key HCC therapeutic area experts within Asia Pacific. A total of 18 oncologists, hepatologists and gastrointestinal specialists (6 HK; 6 SG; 6 TH) participated in the qualitative phase and a total of 55 (15 HK; 20 SG; 20 TH) in the quantitative phase. Face-to-face interviews using a discussion guide (Qualitative phase) were conducted in August to October 2019 and structured questionnaires (Quantitative phase) were implemented in October to November 2019. We are presenting the descriptive statistics of the stage at diagnosis, comorbidities and treatment modalities of HCC patients based upon this study.

Results

The key therapeutic area experts reported that patients in Hong Kong and Singapore present at an advanced stage per the Barcelona Clinic Liver Cancer (BCLC) guidelines (Stage C: 76% HK; 63% SG; 45% TH) as compared to patients in Thailand. Cirrhosis was a key etiology in Singapore and Thailand (90%, 77%) and Hepatitis B in Hong Kong (89%). Targeted therapy was the preferred first-line HCC treatment in Hong Kong, Singapore and Thailand (89%, 84%, 88%). Immunotherapy was the preferred second-line HCC treatment in Hong Kong (64%). Chemotherapy was used first-line in Thailand (13%) and second-line in Hong Kong, Singapore and Thailand (3%, 11%, 24%).

Conclusions

The treatment patterns and presentation of HCC patients at diagnosis varies considerably across Hong Kong, Singapore and Thailand. These findings on real world practice will be useful to clinicians in understanding the trends and patterns in the diagnosis of HCC and developing treatment strategies.

Legal entity responsible for the study

Kantar.

Funding

IPSEN Pharmaceutical company.

Disclosure

P.K.H. Chow: Advisory/Consultancy: Sirtex Medical; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Oncosil; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. J-F. Baladi, Y. Chia, B. Ramaswamy: Full/Part-time employment: Ipsen. V. Grillo, A. Acorda, K. Xu, S. Singh, Y. Chen, Y. Gilliam, R. Gowindah: Full/Part-time employment: Kantar.

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e-Poster Display Session (ID 87) Poster Display

167P - Epidemiology of hepatocellular carcinoma (HCC) in tertiary level hospitals in Bangladesh (ID 776)

Presentation Number
167P
Lecture Time
09:00 - 09:00
Speakers
  • Abdullah Al Mamun Khan (Dhaka, Bangladesh)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

HCC is the most common primary liver malignancy and cause of cancer-related death worldwide and in Bangladesh. It occurs more often in males than females. The incidence of HCC continues to escalate due to HBV, HCV infection, non-alcoholic fatty liver disease (NAFLD). HBV and HCV are also important risk factors for developing chronic liver disease (CLD) and HCC.

Methods

The study was an observational study. All HCC patients in National Institute of Cancer Research and Hospital and Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh from Jan.2010 to Dec.2019 were included. Clinical information and demographic profiles were recorded from departmental documents and retrospectively studied. Patients were arranged as Birch Classification.

Results

Of 1028 patients, 752 (73.15%) were male and 276 (26.85%) were female; M:F was 2.72:1. The average age of HCC onset was 57.9, lowest 23 and highest was 90. The leading age group was ≥60 years, 315 (30.64%) followed by 50-59 year 256 (24.90%), 40-49 year 254 (24.71%). 106 (10.31%) patients presented with metastasis. 688 (66.92%) patients had habitual problems. 478 (46.50%) patients were infected with HBV, 56 (5.45%) were infected with HCV, 632 (61.48%) were suffering from CLD, 180 (17.51%) from NAFLD and only 48 (4.46%) had family histories of malignancy. 240 (23.36%) patients presented with comorbidities. Only 13 (1.26%) were vaccinated against HBV and none had attended for HCC screening. Most patients were poor, 724 (70.43%%) and 683 (66.44%) were illiterate. The leading profession was farmer, 408 (39.69%), followed by housewife, 223 (21.70%).The leading symptom was pain, 348 (33.85%) followed by anorexia, 327 (31.81%), right hypochondriac heaviness, 284 (27.63%). 267 (25.97%) patients presented with impaired liver function, and 339 (32.97%) presented with high alfa feto protein (AFP). 521 (50.68%) patients were on symptomatic treatment prior to attending an oncologist.

Conclusions

HCC is an aggressive cancer and concomitant liver dysfunction with advanced disease impedes curative therapies. HCC can be prevented if appropriate measures are taken, such as HBV vaccination, screening of blood products, use of safe injection practices, treatment and education of alcoholics and drug users.

Editorial acknowledgement

Department of Medical oncology of Shaheed suhrawardy medical college hospital and National Institute of cancer research & hospital

Legal entity responsible for the study

Abdullah Al Mamun Khan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

168P - Response assessments in hepatocellular carcinoma: What are the best criteria to utilize? mRECIST or RECIST 1.1? A retrospective meta-analysis of multiple phase III trials (ID 623)

Presentation Number
168P
Lecture Time
09:00 - 09:00
Speakers
  • Oliver Bohnsack (Berlin, Germany)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In 2010 mRECIST was published in Seminars of Liver Disease for the evaluation of hepatocellular carcinoma (HCC) response assessment. It proposed a modification of existing RECIST 1.1 incorporating visible changes and reduction in the arterial enhancement of the HCC tissue and the concept of measuring viable versus not measuring necrotic tissue, better evaluating treatment responses in HCC with CT or MRI.

Methods

Multiple phase III clinical trials were analyzed using both mRECIST and RECIST 1.1 in parallel, which were read separately by blinded independent central read (BICR). The purpose was to compare the overall response rates and complete response rates by the two criteria. 2601 subjects with 13675 post-baseline imaging timepoints were included in this comparison. The Overall Response Rate (ORR) and the Complete Response Rate (CRR) are derived.

Results

Overall response in 2601 subjects with 13675 time points excluding baseline

mRECIST RECIST 1.1
CR 448 235
PR 2846 2272
SD/NN (Stable Disease/Non-CR Non-PD) 4616 5523
PD (Progressive Disease) 5525 5449
NE 224 180
ORR 24.10% 18.31%
CRR 3.3% 1.7%
.

Conclusions

Our results indicate that: 1.) mRECIST has better ORR and CRR compared to RECIST 1.1. 2.) RECIST 1.1 has more timepoints with Stable Disease SD/NN compared to mRECIST. 3.) mRECIST has more Not Evaluable (NE) timepoints due to more stringent imaging specifications. mRECIST shows almost double the CRR than RECIST 1.1, and the ORR is 33% higher using mRECIST than RECIST 1.1. Stable Disease was observed about 20% more in the RECIST 1.1 analysis, which includes the Non-CR/Non-PD assessment of patients with only non measurable disease for non-target lesions. A reasonable explanation for such a 20% SD discordance being higher with RECIST 1.1 is primarily reflected in the higher number of documented responders assessed with mRECIST. A Non Evaluable (NE) response is more common with mRECIST. Our analysis confirms that mRECIST is more robust in assessing responding patients with CRR and ORR in HCC as it based on measuring the viable tumor component instead of plain linear RECIST 1.1 measurements of its total tumor diameter only.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

169P - IMbrave150: Management of adverse events of special interest (AESIs) for atezolizumab (atezo) and bevacizumab (bev) in unresectable HCC (ID 636)

Presentation Number
169P
Lecture Time
09:00 - 09:00
Speakers
  • Masatoshi Kudo (Osaka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In the phase III IMbrave150 trial, atezo + bev demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) vs sorafenib (sor) in patients (pts) with unresectable HCC. Here we report on the AESIs for both atezo and bev in IMbrave150.

Methods

Eligible pts (N = 501) had unresectable HCC and were randomised 2:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg PO bid until unacceptable toxicity or loss of clinical benefit per investigator. Co-primary endpoints were OS and PFS by independent review facility–assessed RECIST 1.1. AESIs were defined by the sponsor and reported without judgement of causality. AESIs for atezo were based on the immune-mediated risks of atezo and other checkpoint inhibitors; AESIs for bev were based on known adverse drug reactions (ADRs) with bev. Analyses explored the incidence, nature and severity of AESIs as well as corticosteroid use.

Results

The safety-evaluable population included 329 pts in the atezo + bev arm and 156 pts in the sor arm. Median follow-up was 8.6 mo (data cutoff: 29 Aug 2019); median tx durations were 7.4 (atezo), 6.9 (bev) and 2.8 (sor) mo. AESIs for atezo occurred in 69% of pts receiving atezo + bev and also in 82% of pts receiving sor (Table). 12% of pts in the atezo + bev arm vs 3% of pts in the sor arm experienced AESIs requiring systemic corticosteroid tx within 30 days of AE onset. AESIs for bev occurred in 58% of pts receiving atezo + bev and 49% of pts receiving sor. The reported events were ADRs well known with bev, and their frequency and severity were consistent with the safety profile of bev and the underlying disease.

Conclusions

In IMbrave150, AESIs for atezo and bev were manageable. Further, the nature and severity of AESIs were consistent with the known safety profiles of the individual agents and the underlying disease

AESIs, n (%)a Atezo + Bev n = 329 Sor n = 156
All G3-4 All G3-4
For atezo
Pts with ≥ 1 226 (69) 85 (26) 128 (82) 47 (30)
Hepatic eventsb 142 (43) 70 (21) 62 (40) 26 (17)
Inc AST 64 (20) 23 (7) 26 (17) 8 (5)
Inc blood bilirubin 43 (13) 8 (2) 22 (14) 10 (6)
Inc ALT 46 (14) 12 (4) 14 (9) 2 (1)
Ascites 23 (7) 6 (2) 9 (6) 2 (1)
Rash 64 (20) 2 (1) 96 (62) 21 (14)
Hypothyroidism 36 (11) 0 4 (3) 0
Infusion-related reactions 36 (11) 8 (2) 0 0
For bev
Pts with ≥ 1 190 (58) 76 (23) 76 (49) 29 (19)
Hypertension 102 (31) 50 (15) 40 (26) 19 (12)
Bleeding/haemorrhage 83 (25) 21 (6) 27 (17) 9 (6)
Epistaxis 34 (10) 0 7 (5) 1 (1)
Upper GI bleedingc 24 (7) 15 (5) 8 (5) 8 (5)
Proteinuria 70 (21) 10 (3) 13 (8) 1 (1)

Inc, increased. a In ≥ 5% of pts. b ≥ 1 category possible. c Grouped MedDRA PT

.

Clinical trial identification

NCT03434379.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

M. Kudo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self): Bayer; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): BMS; Honoraria (self): Lilly; Honoraria (institution), Research grant/Funding (institution): EA Pharma; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): AbbVie; Advisory/Consultancy: Ono; Advisory/Consultancy: Roche. M. Ikeda: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Teijin; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Bristol-Myers; Research grant/Funding (institution): MSD; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Astellas. A.X. Zhu: Advisory/Consultancy: Lilly; Advisory/Consultancy: Bayer; Advisory/Consultancy: Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Eisai. H.Y. Lim: Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: BMS; Advisory/Consultancy: Ono; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Roche. V. Breder: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Ipsen. P. Merle: Advisory/Consultancy, Ad Board: Bayer; Advisory/Consultancy, Ad Board: Eisai; Advisory/Consultancy, Ad Board: Exelixis; Advisory/Consultancy, Ad Board: Ipsen; Advisory/Consultancy, Ad Board: Lilly; Advisory/Consultancy, Ad Board: Roche; Advisory/Consultancy, Ad Board: AstraZeneca; Advisory/Consultancy, Ad Board: BMS; Advisory/Consultancy, Ad Board: MSD; Advisory/Consultancy, Ad Board: Merck; Advisory/Consultancy, Ad Board: Onxeo. A. Kaseb: Honoraria (self), Research grant/Funding (institution), Research Support: Genentech/Roche; Research grant/Funding (institution), Research Support: BMS; Research grant/Funding (institution), Research Support: Exelixis; Research grant/Funding (institution), Research Support: Bayer; Research grant/Funding (institution), Research Support: AdaptImmune; Research grant/Funding (institution), Research Support: Immatics; Research grant/Funding (institution), Research Support: Merck; Research grant/Funding (institution), Research Support: Eisai. D. Li: Advisory/Consultancy: Genentech. N. Ma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. M. Villalobos: Full/Part-time employment: Genentech/Roche. S. Stanzel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. V.E. Gaillard: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. D-Z. Xu: Full/Part-time employment: Roche. S. Hernandez: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. A-L. Cheng: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Yakuhin; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech/Roche; Honoraria (self): Lilly; Advisory/Consultancy: Bayer Schering Pharma; Advisory/Consultancy: BeiGene, Ltd; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: CSR Pharma Group; Advisory/Consultancy: IQVIA; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono Pharmaceutical. R.S. Finn: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer. P.R. Galle: Honoraria (self): Bayer; Speaker Bureau/Expert testimony: BMS; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Sirtex; Honoraria (self): MSD; Honoraria (self): Ipsen; Honoraria (self): Roche; Advisory/Consultancy: SillaJen; Advisory/Consultancy: Eisai. M. Ducreux: Full/Part-time employment: Sandoz (I); Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Serono; Honoraria (self): MSD Oncology; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self): Roche/Genentech; Honoraria (self), Advisory/Consultancy: Servier; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Merck KGaA; Research grant/Funding (institution): Keocyt. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

170P - Sintilimab plus anlotinib as first-line therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC) (ID 445)

Presentation Number
170P
Lecture Time
09:00 - 09:00
Speakers
  • Xiaofeng Chen (Nanjing, Jiangsu Province, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The synergic combination of anti-PD-1/PD-L1 and antiangiogenic agents has exhibited as an encourage treatment pattern in aHCC. Multi-targeted antiangiogenic TKIs, such as lenvatinib and sorafenib, are approved for 1st-line treatment of aHCC. Sintilimab, a novel selective anti-PD-1 monoclonal antibody, has demonstrated encouraging clinical activities in aHCC. The trial aims to explore the safety and efficacy of sintilimab plus anlotinib (a TKI against angiogenesis) in aHCC.

Methods

This is a single-arm phase II study. Pts with aHCC, BCLC stage C or B (not amenable for surgery and chemoembolization), Child-Pugh scores≤7 and ECOG PS ≤ 1 received 1st-line treatment of sintilimab (200mg, iv, D1) plus anlotinib (12mg, po, QD, D1-14) every 3 wks until disease progression or unacceptable toxicity. Primary endpoints were safety and objective response rate (ORR, per RECIST 1.1), and secondary endpoints included disease control rate (DCR), progression free survival (PFS), duration of response (DOR) and overall survival (OS).

Results

As of June 30, 2020, 16 pts with 14 males, median age 56 yrs (range 41-70), BCLC B /C (3/13), and Child-Pugh A/B7(15/1) were enrolled. All pts received at least two cycles of treatments with median cycles 7 (range 2-18). Median follow-up was 5.3 months (range 2.1-13.3). The most common treatment-related adverse events (TRAEs) were grade 1-2 with thrombocytopenia (50%), increased AST (37.5%), ALT (31.3%) and bilirubin (31.3%), decreased neutrophil count (31.3%), leukopenia (25%), hypertension (25%) and hand-foot syndrome (25%). 6 pts experienced manageable grade 3 TRAEs, and no grade 4/5. 7 pts required dose reduction of anlotinib (4 pts to 10 mg and 3 to 8 mg). No treatment withdraw caused by TRAEs. Of 14 evaluable pts, ORR was 42.9% (6/14) with 1 CR and 5 PR. 7 pts were SD, and DCR was 92.9% (13/14). Median DoR was not reached (95%CI: 9.0 months-not reached), and all the responses were ongoing at the data cutoff. 6m-PFS rate was 78.8% (95%CI: 38.1%-94.3%) and mPFS was unreached.

Conclusions

The combination of sintilimab and anlotinib showed promising clinical activities with manageable toxicity for first line treatment of aHCC. Enrolment is on-going to further validate the combination regimen.

Clinical trial identification

NCT04052152.

Legal entity responsible for the study

Jiangsu Province Hospital - The First Affiliated Hospital with Nanjing Medical University.

Funding

Jiangsu province 333 high level Talents Project; Innovation Funds from Chinese Society of Clinical Oncology Youth Committee. Y-young2019-060; the Advanced Health Talent of Six-One Project of Jiangsu Province. LGY2017069; Joint Research Project by Southeast University and Nanjing Medical University. 3207027381; National Natural Science Foundation of China, 81472306; Key research and development program of Jiangsu Province.BE2016789.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

171P - Transarterial chemoembolization (TACE) plus lenvatinib versus TACE plus sorafenib for hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT): A prospective randomized study (ID 754)

Presentation Number
171P
Lecture Time
09:00 - 09:00
Speakers
  • Xiaoyan Ding (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

HCC with PVTT portends a worse prognosis. This study compared the efficacy and safety of cTACE plus lenvatinib (cTACE+LEN) to the most commonly utilized regimen, cTACE plus sorafenib (cTACE+SOR), in patients with HCC and PVTT.

Methods

An open-label, single-center, prospective, randomized trial. Patients with previously untreated HCC complicated by type I-IV PVTT were randomized 1:1 to receive cTACE+LEN (LEN orally, 12 or 8 mg/d for bodyweight ≥60 or <60 kg) or cTACE+SOR (SOR orally, 400 mg BID). The primary endpoint was time to progression (TTP; time from randomization to disease progression), secondary endpoints included objective response rate (ORR), overall survival (OS) and toxicity. Tumor response was assessed using mRECIST. Prognostic factors were evaluated with a Cox regression analysis. SPSS v17.0 was used for all analyses.

Results

Between Dec 30, 2018 and May 31, 2020, 64 patients were randomized (cTACE+LEN, n=32; cTACE+SOR, n=32). Patients had a median age of 56 years, a male/female ratio of 13/3, the majority had type I/II PVTT (71.9%; n=46), 34.4% (n=22) had extrahepatic metastasis, and median tumor diameter was 9.0 cm (3.8−21.8). After a median follow-up of 12.5 months, patients in the cTACE+LEN group had a higher median TTP (4.7 vs 3.1 months, HR: 0.55 [95% CI: 0.32–0.97], P=0.037) and numerically higher ORR (50.0 vs 25.0%, P=0.07) and median OS (15.6 [95% CI: 7.7−23.5] vs 10.8 months [95% CI: 8.9−12.7], P=0.15) versus the cTACE+SOR group. A similar incidence of serious adverse events (n=4 vs 2, including gastrointestinal bleeding and hepatic failure), drug withdrawal and dose reduction occurred in the cTACE+LEN and cTACE+SOR groups, and no treatment-related deaths occurred during the study period. Objective response was identified as an independent predictor of favorable TTP (HR: 0.41 [95% CI: 0.22–0.75], P=0.004).

Conclusions

cTACE+LEN was safe, well-tolerated, and had favorable efficacy versus cTACE+SOR for the treatment of advanced HCC with PVTT and large tumor burden. Differences in ORR and OS did not reach statistical significance, which may be due to the limited sample size and requires further study.

Clinical trial identification

NCT04127396.

Legal entity responsible for the study

Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Funding

Beijing Hospitals Authority, QML20191805.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

172P - Triple combination therapy of lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy versus lenvatinib for advanced hepatocellular carcinoma (ID 431)

Presentation Number
172P
Lecture Time
09:00 - 09:00
Speakers
  • Zhi-Cheng Lai (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC), but the prognosis was still unsatisfactory. Recently, hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors have shown promising results for patients with advanced HCC. Considering different anti-malignancy mechanisms, combining these three modalities may improve outcomes. This study was to compare the efficacy and safety of lenvatinib, toripalimab, plus HAIC versus lenvatinib alone for advanced HCC patients.

Methods

This was a retrospective study including patients treated with lenvatinib alone (8 mg [≤60kg] or 12mg [>60kg] once daily) or lenvatinib, toripalimab plus HAIC (LeToHAIC group, lenvatinib once daily 0-1 week prior to initial HAIC, 240 mg toripalimab 0-1 day prior to every HAIC cycle, and HAIC with FOLFOX regimen [oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks]). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse event (TRAE) were compared.

Results

From February 2019 to August 2019, 157 patients were included for this study: 71 in the LeToHAIC group, and 86 in the lenvatinib group. The LeToHAIC group showed a longer PFS (11.1 vs 5.1 months, p<0.001), a longer OS (not reached vs 11 months, p<0.001), a higher DCR (RECIST or mRECIST: 90.1% vs 72.1%, p=0.005), a higher ORR (RECIST: 59.2% vs 9.3%, p<0.001; mRECIST: 67.6% vs 16.3%, p<0.001) than the lenvatinib group. In addition, 14.1% of patients in the LeToHAIC group achieved complete response by mRECIST criteria. Grade 3/4 TRAEs that were more frequent in the LeToHAIC group than in the lenvatinib group included neutropenia (8.5% vs 1.2%), thrombocytopenia (5.6% vs 0), and nausea (5.6% vs 0).

Conclusions

Triple combination therapy of lenvatinib, toripalimab, and HAIC had acceptable toxic effects and might improve survival compared with lenvatinib alone in advanced HCC.

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China Ministry of Science and Technology of the People's Republic of China.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

173P - Regorafenib in patients (pts) with unresectable hepatocellular carcinoma (uHCC) in real-world practice in Asia: Interim results from the observational REFINE study (ID 606)

Presentation Number
173P
Lecture Time
09:00 - 09:00
Speakers
  • Ho Yeong Lim (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In the phase III RESORCE trial, regorafenib improved overall survival (OS) vs placebo in pts with uHCC who progressed on sorafenib. The international, prospective REFINE study was designed to evaluate regorafenib in pts with uHCC in routine practice. We present interim results for pts enrolled in REFINE in Korea, China, and Taiwan.

Methods

REFINE is an ongoing observational study that recruited patients with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment according to the local health authority approved label. A planned interim analysis was performed when the first 500 pts in the global cohort had been observed for ≥4 months. The primary aim is to assess treatment-emergent adverse events (TEAEs; NCI-CTCAE v4.03). Secondary endpoints include OS, progression-free survival, and tumor response. Tumor response and progression are assessed per investigator according to local standard.

Results

In the interim analysis, a total of 182 pts were enrolled from Korea (n=127; 70%), China (n=48; 26%), and Taiwan (n=7; 4%). The median age was 60 years (range 21–90); 80% were male. At study entry, proportions of pts with ECOG performance status 0/1/≥2 were 37%/49%/5%; proportions with Child–Pugh A/B/C class were 70%/5%/1% (missing/not evaluable: 24%). The initial daily regorafenib dose was 160 mg in 70% of pts and 120 mg/80 mg in 14%/15%; 1 pt started at 40 mg. The mean initial daily dose was 142 mg (standard deviation 31). Median treatment duration was 3.2 months (interquartile range 1.9–9.3). The most frequent TEAEs (reported in ≥5% patients) are shown in the table. Effectiveness results will be presented.

Conclusions

In this interim analysis of pts from Asia in the observational REFINE study, the TEAEs reported were consistent with those reported in the phase III RESORCE trial, although incidence rates of some TEAEs were lower than in RESORCE

TEAE, % Regorafenib (n=182)
Any grade Grade 3 Grade 4
Hand–foot skin reaction 29 1 -
Diarrhea 14 2 0
Decreased appetite 9 1 0
Abdominal pain 7 3 0
Hypertension 6 2 0
Fatigue 5 1 -
.

Clinical trial identification

NCT03289273.

Editorial acknowledgement

Editorial assistance in the writing of this abstract was provided by Jennifer Tobin of OPEN Health Medical Communications (Choice), with financial support from Bayer.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

H.Y. Lim: Advisory/Consultancy: Bayer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ono Pharmaceutical. Y.J. Kim: Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): BTG; Honoraria (self): Bayer; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy, Resarch grant/Funding (self): Gilead Sciences; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Roche. Y-H. Huang: Advisory/Consultancy: Gilead Sciences; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: Bayer. C-H. Hsu: Honoraria (self), Advisory/Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Genentech; Advisory/Consultancy: Merck Serono. H.C. Lee: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Bayer; Research grant/Funding (self): Roche; Research grant/Funding (self): Merck; Research grant/Funding (self): Bristol-Myers Squibb. S. Fiala-Buskies: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer. S. Kapur: Full/Part-time employment: Bayer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

174P - A real-world study of PD-1 inhibitors combined with TKIs for HCC with major vascular invasion as the conversion therapy: A prospective, non-randomized, open-label cohort study (ID 508)

Presentation Number
174P
Lecture Time
09:00 - 09:00
Speakers
  • Wenwen Zhang (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Hepatocellular carcinoma (HCC) patients with major vascular invasion (MVI) were generally recommend systemic treatment by guidelines, while some data showed R0 resection can improve survival than local treatment. Conversion therapy using immune checkpoint inhibitors may benefit these patients in the context of cancer immunotherapy. Here we report a prospective real-world study of PD-1 inhibitors in combination with tyrosine kinase inhibitors (TKIs) as a conversion therapy for HCC with MVI.

Methods

Briefly, the main inclusion criteria of the study (ChiCTR1900023914) was: Aged 18 to 75 years HCC patients diagnosed pathologically and/or radiologically, with at least one measurable lesion (mRECIST) and MVI. The criteria for Successful Conversion: 1. Child-Pugh score < 7. 2. ECOG PS score ≤1. 3. No extrahepatic lesion. 4. Intact vascular structure of the reserved liver and sufficient FLR.

Results

70 Patients were screened, and 39 patients enrolled in the study by May 20, 2020. Among them 35 patient accepted the combination therapy (Primary HCC n=31, Recurrence after local treatment n=4), in which 30 patients with PVTT, 2 with venous tumor thrombi and 3 with both. A total of 33 patients were assessable. The response evaluation according to mRECIST standard was in table below. Successful conversion rate based on radiology was 42.4% (14/33).

Summary of response evaluation and conversion rate

Best objective response, n Total, n
CR n=5 PR n=10 SD n=12 PD n=6 33
Successful Conversion, n 5 7 1 1 14
Reasons for not conversion Inadequate FLR n=2, Poor CTP n=1 Inadequate FLR n=11 Inadequate FLR n=5
Patients underwent subsequent surgery, n 4 3 1 1 9
Pathological evaluation of response pPR: 1/4 pPD: 2/3 pSD pPD
.

The subsequent salvage surgery was all en-bloc R0 resection of both tumor and PVTT. No complications beyond Clavien-Dindo level III or postoperative mortality were observed. The median follow-up time was 7.2 months. The median relapse free survival and median overall survival was 3.9 months and 6.5 months respectively. Patients with pPD had a worse prognosis.

Conclusions

The combination therapy of PD-1 inhibitors and TKIs can be reviewed as a reasonable and promising conversion therapy option for advanced HCC with safety and effectiveness. Furthermore, pathology can confirm the response evaluation and guide subsequent treatment more precisely.

Clinical trial identification

ChiCTR1900023914.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

175P - A study of neoadjuvant sintilimab combined with triplet chemotherapy of lipo-paclitaxel, cisplatin, and S-1 for resectable esophageal squamous cell carcinoma (ESCC) (ID 596)

Presentation Number
175P
Lecture Time
09:00 - 09:00
Speakers
  • Yanhong Gu (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Although preoperative chemoradiotherapy is the standard of care for patients (pts) with resectable locally advanced esophageal cancer, ESCC still has a dismal prognosis. PD-1 blockade has demonstrated significant clinical benefits in metastatic ESCC (ORIENT-02), and the addition of PD-1 to chemotherapy improved clinical outcomes in other squamous cell malignancies, such as lung and head & neck cancer. This trial (KEEP-G 03) evaluates the feasibility and safety of preoperative sintilimab (anti-PD-1) in combination with triplet chemotherapy in resectable ESCC.

Methods

This is a single-arm, phase Ib/II trial. Pts with histopathologically confirmed resectable (T1b-T3,N0-N+M0, AJCC 8th) ESCC were enrolled. Sintilimab (200mg, iv, d1) in combination with lipo-paclitaxel (135 mg/m2, iv, d1), cisplatin (25mg/m2, iv, d1-3), S-1 (40mg po, bid, d1-14) were given for 2 cycles every 3wks, followed by esophagectomy. The primary objectives were feasibility and safety (CTCAE 5.0), and secondary objectives included MPR, pCR, R0 rate, RFS, and OS.

Results

From 5/2019 to 6/2020, 17 pts were enrolled. The median age was 65 yrs (range 42-69), 76.4% were male, and 70.6% had an ECOG PS 1. The proportions of cT- and cN- stage were T2 23.5%, T3 76.5%, and N0 94.1%, N1 5.9%. All pts completed neoadjuvant treatment and 15 have completed esophagectomy stick to schedule (≤6wks) with 100% R0 resection. 2 pts were waiting for planned surgery at time of abstract. No pts failed to proceed to surgery. And no unexpected surgical complication was observed. Grade 3/4 TRAEs (35.3%) were leukopenia, neutropenia, and anemia. 1 pts experienced grade 1 rash suspicious of immune-related. Of note, 4 out of 15 achieved pCR (26.7%) and 8 achieved MPR (53.3%).

Clinical TNM staging, pathologic findings and pathologic remission

No. Pre-treatment clinical TNM staging Post-treatment radiological TNM staging Post-treatment pathological staging Post-treatment residual viable tumor (%)
1 cT2N0M0 ycT2N0M0 ypT3N0M0 90
2 cT2N0M0 ycT2N0M0 ypT1bN0M0 2
3 cT3N0M0 ycT2N0M0 ypT3N0M0 8
4 cT3N0M0 ycT2N0M0 ypT0N0M0 0
5 cT3N0M0 ycT3N0M0 ypT3N0M0 85
6 cT3N0M0 ycT2N0M0 ypT3N0M0 80
7 cT3N0M0 ycT3N0M0 ypT3N0M0 90
8 cT3N0M0 ycT2N0M0 ypT1bN0M0 1
9 cT3N0M0 ycT2N0M0 ypT3N0M0 75
10 cT3N0M0 ycT1N0M0 ypT0N0M0 0
11 cT2N0M0 ycT1N0M0 ypT0N0M0 0
12 cT3N0M0 ycT3N0M0 ypT0N0M0 0
13 cT2N0M0 ycT4N1M0 ypT3N1M0 90
14 cT3N1M0 ycT2N0M0 ypT3N0M0 2
15 cT3N2M0 ycT3N2M0 ypT3N2M0 90
.

Conclusions

Given the encouraging MPR and pCR and favorable tolerability, the regimen of sintilimab plus triplet chemotherapy could be a feasible and safe neoadjuvant option for locally advanced ESCC.

Clinical trial identification

NCT03946969.

Legal entity responsible for the study

Department of Oncology and Cancer Rehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Funding

National Natural Science Foundation of China (Nos. 81871944) and Jiangsu Province Key Medical Talents (Nos. ZDRCA2016026).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

176P - Effect of adjuvant lenvatinib (LEN) on tumour recurrence in patients with hepatocellular carcinoma (HCC) and high residual alpha-fetoprotein (AFP) following resection or ablation: A single-center, retrospective study (ID 614)

Presentation Number
176P
Lecture Time
09:00 - 09:00
Speakers
  • Liang Cai (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In China, surgical resection and ablation are widely used to treat HCC; however, relapse rates are high for patients with residual elevated AFP 2 months post-treament. LEN has been shown to reduce AFP levels in patients with advanced HCC. We therefore investigated the efficacy of LEN for preventing recurrence in patients with HCC and elevated AFP after surgery or ablation.

Methods

This single-center, retrospective study, conducted between Nov 2018 and Jan 2020, included medical records from 84 patients with HCC who achieved complete radiologic response following resection or radiofrequency ablation, had high residual AFP (>20 ng/mL) 8 weeks post-surgery and received LEN according to local labelling (n=23), adjuvant transarterial chemoembolization (TACE; n=25) or no treatment (Control group, n=36). A further group of patients with HCC R0 resection (AFP negative post-surgery) was also included (n=22). AFP response was defined as >20% reduction in AFP ≤8 weeks from initiation of LEN. Recurrence free survival (RFS) was calculated from initiation of treatment (LEN and TACE groups) or the date of surgery (Control and R0 groups) until first confirmed local, regional or distant tumor recurrence.

Results

Median follow-up in all patients was 11.2 months. Patient baseline characteristics were similar between groups, except for baseline BCLC stage. Among patients receiving LEN, 61% (14/23) achieved an AFP response. The rate of 1-year RFS was higher for patients in the LEN group who achieved an AFP response (71.4% [10/14]) compared with the TACE (36.0% [9/25]) and Control (50.0% [18/36]) groups. Median RFS had not been reached in the LEN, TACE, and R0 groups. At data cutoff, 9 (64.3%) patients receiving LEN who achieved an AFP response were recurrence free, and follow-up is on-going.

Conclusions

LEN led to an AFP response in 61% of patients with HCC and residual elevated AFP post surgery/ablation, and this was associated with a high 1-year RFS. Therefore, AFP response may provide a biomarker to predict response to LEN in this setting and further investigation in prospective trials is warranted.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

177P - Organ specific tumour response to first-line (1L) therapy with combined lenvatinib (LEN) and anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma (HCC) (ID 727)

Presentation Number
177P
Lecture Time
09:00 - 09:00
Speakers
  • Hui-Chuan Sun (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Clinical trials of combined LEN and anti-PD-1 antibodies in advanced HCC have shown promising anti-tumor effects. Although responses of both intra- and extra-hepatic tumors are typically evaluated to assess efficacy of a systemic therapy in HCC, the responses of tumors in different sites or organs can be very heterogeneous.

Methods

A retrospective analysis of patients with advanced, unresectable HCC who received 1L LEN (8 mg/d regardless of bodyweight) plus anti-PD-1 antibodies either q2wk (nivolumab or camrelizumab) or q3wk (pembrolizumab, sintilimab or toripalimab). Patients who completed ≥1 efficacy and safety assessment were eligible for inclusion. Overall objective response rate (ORR) and organ-specific response rate (OSRR) were assessed using RECIST 1.1 and mRECIST. All evaluations were repeated by an independent imaging reviewer.

Results

From Oct 2018 to Mar 2020, 59 patients were assessable for efficacy (median age: 54.3 years; 91.5% males). Among these patients, 2 (3.4%) were BCLC stage A, 11 (18.6%) were BCLC stage B, and 46 (78.0%) were BCLC stage C (including 30 with macroscopic vascular invasion, [China Liver Cancer [CNLC] stage IIIa] and 16 with extrahepatic metastasis or combined with macroscopic vascular invasion [CNLC stage IIIb]). The overall ORR evaluated using RECIST 1.1 and mRECIST was 32.2% and 57.6% according to investigator review, and 33.9% and 50.8% according to independent imaging review, respectively. OSRR was higher in macrovascular tumor thrombi (MVTT, including portal vein and hepatic veins) versus other sites (Table). Five patients with MVTT were successfully converted to liver resection because of downstaging via significant response in MVTT.

Objective response rate, % RECIST v1.1 (investigator) RECIST v1.1 (independent imaging review)
Overall (n=59) 32.2 33.9
Organ-specific
Liver (n=57) 33.0 32.0
Macrovascular tumor thrombi (n=33) 57.5 51.5
Lung (n=7) 37.5 37.5
Lymph node (n=6) 33.3 33.3
Adrenal gland (n=2) 100 100
Intra-abdominal implantation (n=2) 100 100
.

Conclusions

The response of MVTT to combined LEN and anti-PD-1 antibodies was higher versus HCC tumors in other sites. The mechanisms underlying this differential response warrant further investigation.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

178P - Real-world efficacy and safety of lenvatinib in Korean patients with advanced hepatocellular carcinoma: A multicenter retrospective analysis (ID 144)

Presentation Number
178P
Lecture Time
09:00 - 09:00
Speakers
  • Jaekyung Cheon (Ulsan, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lenvatinib (LEN) has demonstrated the efficacy and safety in patients (pts) with advanced HCC (aHCC) as first-line treatment in the pivotal REFLECT trial. Further evaluation in real-world setting is necessary to measure the clinical outcomes of LEN in daily practice.

Methods

This is a multicenter retrospective analysis from 3 Korean referral cancer institutions. Between September 2018 and November 2019, a total of 86 pts received LEN for the management of BCLC B or C aHCC, and 75 pts who had at least one follow-up visit after the start of LEN were included in this analysis.

Results

Median age was 59 years (range, 19-81), and 56 pts (74.7%) were male. Baseline characteristics were as follows; Child-Pugh class A/B in 57 (76.0%)/18 (24.0%), BCLC B/C in 9 (12.0%)/66 (88.0%), prior systemic therapy in 24 (32.0%) including 14 (18.7%) with prior immune checkpoint inhibitors (ICIs). LEN was used as 1st/2nd/3rd-4th lines of therapy in 51 (68.0%)/13 (17.3%)/11 (14.7%) pts, and 30 (40.0%) had extensive disease extent excluded in the REFLECT trial. In overall pts, the median follow-up duration was 4.7 months (mo) (95% CI, 3.3-6.2), the median PFS and OS were 4.6 (95% CI, 3.6-5.6) and 6.7 mo (95% CI, 5.0-8.3), repectively. In Child-Pugh A group, the PFS and OS were as follows: 1st line setting, 4.6 (95% CI,3.1-6.1) and 10.7 mo (95% CI, 4.7-16.6); >= 2nd line setting, 4.4 (95% CI, 2.8-6.0) and 6.4 mo (95% CI,4.7-8.0); prior ICI group 4.4 (95% CI, 3.6-5.1) and 7.1 mo (95% CI, 5.7-8.5), respectively. In Child-Pugh B group, the PFS and OS were 2.6 (95% CI, 0.6-4.6) and 5.3 mo (95% CI, 2.0-8.5), respectively. According to the RECIST v 1.1, response rates and disease control rate were 10.7% and 77.4%, respectively, in overall pts. The most common grade 3-4 toxicities were hyperbilirubinemia (n=8, 10.7%), AST elevation (n=6, 8.0%) and diarrhea (n=4, 5.3%).

Conclusions

LEN was effective and well tolerated in pts with aHCC in Korean real-life setting.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Yoo: Advisory/Consultancy: Bayer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: MSD. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

179P - Regorafenib combined with transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC) with previous systematic treatment: A preliminary investigation of safety and efficacy (ID 699)

Presentation Number
179P
Lecture Time
09:00 - 09:00
Speakers
  • Yue Han (Peking, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

HCC is the fourth most common malignancy in China, and ranks second by mortality rate. Most patients have already reached advanced stage when diagnosed. TACE in combination with first-lined systematic therapy has been explored as an effective treatment for unresectable HCC. However, it has not been reported the safety and efficacy of Regorafenib combined with TACE, as a second-lined therapy. In this multicenter retrospective study, we preliminarily investigated the safety and efficacy of a combination with Regorafenib and TACE therapy in patients with unresectable HCC.

Methods

We reviewed the medical data of 38 patients with progression after prior treatment of Sorafenib and/or Lenvatinib from Jan 2019 to Apr 2020 at 4 tertiary centers in China. Patients were treated with TACE initially after enrollment. 5-7 days after the first TACE, patients started taking Regorafenib PO for 3 weeks on/1 week off. All patients were required to be followed up regularly and TACE was repeated as needed. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), drugs safety, adverse events (AEs) were observed. OS was calculated from date of first TACE to death. TTP was calculated from date of first TACE to progression. Adverse events were evaluated by Clavien classification. Drugs safety was investigated according to CTCAE v4.03.

Results

Baseline patient characteristics are presented in the table

Baseline patient characteristics

Baseline characteristic Total (n=38)
Age (years) 59.4±9.19
Sex, n (%)
Male 32 (84.2%)
ECOG, n (%)
0 21 (55.3%)
1 13 (34.2%)
2 4 (10.5%)
BCLC, n (%)
B 18 (47.4%)
C 20 (52.6%)
Hepatitis, n (%)
HBV 32 (84.2%)
HCV 2 (5.3%)
No 4 (10.5%)
Maximum tumor size (cm) 3.75 (2.5, 7.5)
Tumor number, n (%)
1 4 (10.5%)
≥2 34 (89.5%)
AFP (μg/L) 50.85 (6.64, 1210)
Extrahepatic metastasis, n (%) 13 (34.2%)
Portal vein invasion, n (%) 12(31.6%)
Prior Local Therapy, n (%)
Surgery 13 (34.2%)
Ablation 20 (52.6%)
TACE 36 (94.7%)
Radiotherapy 6 (15.8%)
Follow-up, months(range) 5.6 (1.7,17.0)
Prior Systemic Therapy, n(%) Sorafenib Lenvatinib Lenvatinib Sequential to Sorafenib 33 (86.8%) 1(2.6%) 4(10.5%)
. After enrollment, all patients were treated with conventional TACE, with an average of 3 sessions. The initial daily dose of Regorafenib was 80mg (26.3%), 120mg (44.7%) and 160mg (28.9%), respectively. Within all the study population, the overall incidence of AEs was 47.4%, and the most common AE was hand-foot syndrome (15.8%). The incidence of grade 3/4 AEs was 15.8%, and only 5 patients were halted due to intolerance. No patient experienced severe complications after the procedure. By now, the median duration of follow-up was 5.6 months and median OS was 14.3 months. The median PFS and TTP were 7.4 months (95%CI:3.0, 11.8) and 9.1 months(95%CI:5.4, 12.8), respectively.

Conclusions

Regardless of the retrospective nature, the present study as the first up-to-date real-world evidence indicates that Regorafenib combined with TACE was clinically effective and tolerable in subsequent to prior systemic therapy for unresectable HCC. Additional prospective large-scale studies are required to further verify our conclusion.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

180P - Real-world (RW) treatment (tx) patterns and outcomes in patients (pts) from Taiwan and Singapore with intermediate and advanced hepatocellular carcinoma (HCC) (ID 591)

Presentation Number
180P
Lecture Time
09:00 - 09:00
Speakers
  • Su Pin Choo (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

HCC is a leading global cause of cancer mortality, particularly in the Asia-Pacific region (APAC). An understanding of RW tx patterns and outcomes in APAC may inform current disease management. Here we report tx patterns and survival outcomes in a RW population of pts from Taiwan and Singapore with intermediate/advanced HCC.

Methods

This secondary data study from the HCC Registry in Asia (NCT03233360) used third-party (IQVIA) de-identified pt-level data collected retrospectively and prospectively from electronic health records from Taiwan and Singapore, including for pts newly diagnosed with HCC from Jan 2013 to Dec 2019. Descriptive statistics were used to summarize tx patterns (sequence, frequency) and pt characteristics by country and BCLC staging B or C; the Kaplan-Meier method was used to estimate median overall survival (mOS).

Results

Pt characteristics by stage and country are in the table. In Singapore in pts with BCLC B (n = 26), TARE/Y90 was the most common 1st tx (50%) followed by resection (19.2%). In BCLC C pts (n = 22) systemic therapies were common (68.2%). In Taiwan, BCLC B pts (n = 51) were often treated with resection (43.1%) or TACE (31.4%); BCLC C pts (n = 46) were most often treated with systemic therapy (41.3%). mOS in BCLC B pts was 21 mo in Singapore and 25 mo in Taiwan. In BCLC C pts mOS was 4 mo in Singapore and 6 mo in Taiwan.

Conclusions

This study showed utilization patterns of available tx options in and characteristics of HCC pts in Singapore and Taiwan despite the limited sample size. HCC RW data from APAC are scarce. This registry’s data collection, still ongoing outside Taiwan and Singapore, provides useful insights into RW practice and outcomes and illustrates urgent need for new tx options for HCC. As new txs emerge such as atezolizumab + bevacizumab for 1st line tx of unresectable or metastatic HCC, future RW studies extending this work will help reveal their RW impact on pts

Pt characteristics, tx frequency and tx sequence in Singapore and Taiwan

BCLC stage Singapore Taiwan
B C B C
Pts, n 26 22 51 46
Age, years, median (IQR) 66.0 (62.8-70.6) 64.0 (60.0-67.8) 65.4 (57.1-73.1) 63.1 (55.7-68.1)
Male, n (%) 24 (92.3) 15 (68.2) 42 (82.4) 37 (80.4)
Hepatitis B positive, n (%) 8 (30.8) 12 (54.5) 30 (58.8) 23 (50.0)
Pts with subsequent tx, n 8 6 3 10
Most common subsequent tx (%)a Syst ther (50.0) Syst ther (83.3) LRT (66.7) Syst ther (90.0)

BCLC, Barcelona Clinic Liver Cancer; LRT, locoregional therapy; Syst ther, systemic therapy; TACE, transarterial chemoembolization; TARE/Y90, transarterial radioembolization with yttrium-90 a % calculated among all pts receiving a subsequent tx

.

Clinical trial identification

NCT03233360.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Chris Lum, PhD of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

S.P. Choo: Honoraria (self), Advisory/Consultancy: eisai; Honoraria (self), Advisory/Consultancy: Bristol Myers Squibb; Speaker Bureau/Expert testimony: DKSH; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Ipsen. S.K. Mhatre: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech, Inc. A. Ferro: Full/Part-time employment: Genentech/Roche. R. Machado, D.H-C. Liu, N. Irahara: Full/Part-time employment: Roche. V.E. Gaillard: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

181P - Evaluation of first-line systemic treatments for unresectable hepatocellular carcinoma (uHCC): A network meta-analysis (ID 821)

Presentation Number
181P
Lecture Time
09:00 - 09:00
Speakers
  • Weihua Zhi (Peking, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Based on the phase III REFLECT study, lenvatinib (LEN) has been recommended as a first-line (1L) therapy for uHCC since 2018. Recent years have seen a further expansion of 1L treatment recommendations for uHCC, to include atezolizumab+bevacizumab, nivolumab, FOLFOX4 and donafenib. We conducted a network meta-analysis (NMA) to compare the efficacy and safety of lenvatinib with other systemic therapies in first-line uHCC.

Methods

A systematic literature review identified randomized, controlled, multicenter trials in adults with advanced HCC who had received no prior systemic therapy. Literature retrieval was conducted using PubMed, ScienceDirect, the Cochrane Database, EMBASE and other sources. Objective response rate (ORR), disease progression-free survival (PFS), time-to-progression (TTP) and treatment discontinuations due to adverse events (AEs) were extracted from published studies and quantitatively pooled using frequentist NMA. Pairwise risk ratio(RR), hazard ratio(HR) with confidence interval was calculated. The P-scores were used to rank each treatment.

Results

In total, 1398 records were screened and 27 were eligible for analysis, and the treatments included were atezolizumab+bevacizumab, brivanib, FOLFOX4, donafenib, dovitinib, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies and three other combination therapies. For ORR and TTP, lenvatinib was ranked first (P-scores: 0.88 and 0.99), for PFS, atezolizumab+bevacizumab was ranked first followed by lenvatinib (HR: 0.89; 95% CI, 0.64-1.25; P-scores: 0.95 and 0.90) and donafinib and nivolumab ranked 5th and 6th (HR: 1.38; 95% CI, 1.09-1.73, HR: 1.41; 95% CI, 1.13-1.76; P scores: 0.90 vs 0.59 vs 0.56 respectively). Atezolizumab+bevacizumab was associated with the highest probability of discontinuation due to AEs (RR: 1.27 [0.35-4.60]), lenvatinib ranked 4th (P scores: 0.25 and 0.39, respectively).

Conclusions

This NMA suggested that greater ORR and TTP benefits with first-line use of Lenvatinib than others. Although Atezolizumab+Bevacizumab showed more benefit in PFS, more discontinuation because of AE should also take into consideration.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

183P - Textbook outcome as a measure of surgical quality assessment and prognosis in gastric neuroendocrine carcinoma: A large multicenter sample analysis (ID 736)

Presentation Number
183P
Lecture Time
09:00 - 09:00
Speakers
  • You-Xin Gao (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Quality assurance is crucial for oncological surgical treatment assessment. For rare diseases, single-quality indicators are not enough. To develop a comprehensive and reproducible measurement, called the "Textbook Outcome” (TO), to assess the quality of surgical and prognosis of gastric neuroendocrine carcinoma (G-NEC) patients.

Methods

Data from patients with primary diagnosed gastric neuroendocrine neoplasms (G-NEN) included in the Study Group for Gastric Neuroendocrine Tumors (involving 24 high-volume Chinese hospitals, October 2005-September 2018) were analyzed. After applying the exclusion criteria, 860 G-NEC patients were included in this study. TO included receiving a curative resection, ≥15 lymph nodes (LNs) examined, no severe postoperative complication, hospital stay ≤21 days, and no hospital readmission ≤30 days after discharge. A Sankey plot displayed changes between TO and long-term survival. Hospital variation in TO was analyzed using a case mix-adjusted funnel plot. Prognostic factors for survival and risk factors for non-TO were analyzed using Cox and logistic regression analyses, respectively.

Results

TO was achieved in 56.6% of G-NEC patients. TO patients had better overall (OS), disease-free (DFS), and recurrence-free (RFS) survivals than non-TO patients (P <0.05). Sankey plot showed that the prognostic outcome of most TO patients flowed to alive (62.1%). Moreover, TO patients accounted for 60.3% of patients without recurrence. Multivariate Cox analysis revealed non-TO as an independent risk factor for OS, DFS, and RFS of G-NEC patients (P <0.05). Increasing TO rates were associated with improved OS for G-NEC patients, but not hospital volume. Multivariate logistic regression revealed that non-lower tumors, open surgery, and >200 ml blood loss were independent risk factors for non-TO patients (P <0.05).

Conclusions

TO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients. Factors predicting non-TO are identified, which may help guide strategies to optimize G-NEC outcomes.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

184P - Development and external validation of a nomogram to predict recurrence-free survival after R0 resection for stage II/III gastric adenocarcinoma: An international multicenter study (ID 464)

Presentation Number
184P
Lecture Time
09:00 - 09:00
Speakers
  • Bin-Bin Xu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC.

Methods

Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n=1240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n=306) and a US cohort (n=111), respectively.

Results

The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram’s predictive performance was confirmed in both the internal and external validation cohorts.

Conclusions

A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

185P - Effect of sarcopenia on short- and long-term outcomes of patients with gastric neuroendocrine tumour after radical surgery: Results from a large, two-institutional series (ID 716)

Presentation Number
185P
Lecture Time
09:00 - 09:00
Speakers
  • Ling-Qian Wang (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The relationship between sarcopenia and prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy.

Methods

This study retrospectively collected data of 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression were used to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS).

Results

In this study, there were 59 patients (42.8%) with sarcopenia. Among the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9% and 30.4%, of serious postoperative complications 0% and 3.7%, of postoperative surgical complications 13.6% and 15.2%, of postoperative systemic complications 20.3% and 15.2% (all p>0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS:42.37% vs 65.82%, p=0.004; RFS:52.54% vs 68.35%, p=0.036). Multivariate analysis showed that sarcopenia was related to long-term prognoses of g-NENs patients. A stratified analysis based on pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p=0.007; RFS: 51.43% vs 74.36%, p=0.026); furthermore, multivariate analysis showed that sarcopenia was an independent risk factor for gMANEC patients (p<0.05).

Conclusions

Sarcopenia is not related to short-term prognoses of g-NENs patients. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

186P - Characterization of the gastroenteropancreatic neuroendocrine tumour patient journey (ID 611)

Presentation Number
186P
Lecture Time
09:00 - 09:00
Speakers
  • George A. Fisher Jr (Stanford, CA, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

With increasing incidence and prevalence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs), there is a need to identify inefficiencies in patient management.

Methods

To provide a view of the journey for patients with GEP-NETs, healthcare professionals (HCPs) and patients from the USA and EU4 (France, Italy, Spain, UK) were interviewed with responses analyzed to determine consensus views.

Results

Fifty-four interviews were completed (49 HCPs, five patients). Time to first diagnosis of GEP-NET takes 5–7 years on average and misdiagnosis is common. Multidisciplinary team (MDT) structure and dynamics vary by practice type, institution, and country. In academic settings, GEP-NET is discussed in gastroenterology and/or hepatobiliary tumour boards, but centres with large case volume may hold NET-specific MDTs. Nuclear medicine physicians are increasingly involved in MDTs across many institutions, where they are consulted on patient eligibility for peptide receptor radionuclide therapy (PRRT). In the USA, medical oncologists are the primary treatment decision-makers, while gastroenterologists and endocrinologists are more involved in decisions in Europe, depending on tumour localization. Surgery-ineligible first-line cases are widely managed with somatostatin analogue therapy, and systemic options including PRRT and liver-directed therapies are provided for patients with metastatic disease. While PRRT is commonly used in second-line for low grade, well differentiated tumors, it can be considered in first-line for patients with poorly differentiated fast-growing, somatostatin receptor-positive tumours. Treatment sequencing depends highly on physician attitudes and logistical barriers. HCP follow-up varies according to treatment and experience with GEP-NET.

Conclusions

The rarity of GEP-NET, along with its late diagnosis and misdiagnosis can lead to complexities and uncertainty in sequencing when selecting the right therapy. Differences in management decision vary amongst institutions and countries, and the involvement of nuclear medicine physicians in the decision-making process of MDTs can improve awareness to availability of a treatment option such as PRRT.

Editorial acknowledgement

Under the guidance of the authors, Dr Martin Guppy from Oxford PharmaGenesis provided medical writing support for this abstract, with funding from Advanced Accelerator Applications, a Novartis Company.

Legal entity responsible for the study

Advanced Accelerator Applications SA, a Novartis Company.

Funding

Advanced Accelerator Applications SA, a Novartis Company.

Disclosure

G.A. Fisher Jr: Honoraria (self): Advanced Accelerator Applications; Honoraria (self): Ipsen; Research grant/Funding (self): Genentech/Roche; Research grant/Funding (self): Aduro; Research grant/Funding (self): Xencor; Research grant/Funding (self): FortySeven; Advisory/Consultancy: Merck; Advisory/Consultancy: Taiho; Advisory/Consultancy: Pfizer; Officer/Board of Directors, Data Safety Monitoring Board: AstraZeneca; Officer/Board of Directors, Data Safety Monitoring Board: Hutchison MediPharma International. V. Nassiri: Full/Part-time employment: Advanced Accelerator Applications, a Novartis company; Shareholder/Stockholder/Stock options: Novartis. F. Erman: Full/Part-time employment: Advanced Accelerator Applications; a Novartis Company. S. Mutevelic: Full/Part-time employment: Advanced Accelerator Applications; a Novartis Company; Shareholder/Stockholder/Stock options: Novartis.

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e-Poster Display Session (ID 87) Poster Display

187P - More is not always better: A multicenter study in lymphadenectomy during gastrectomy for gastric neuroendocrine carcinoma (ID 694)

Presentation Number
187P
Lecture Time
09:00 - 09:00
Speakers
  • Qi-Yue Chen (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Few reports address the impact of surgery on the prognosis of rare and heterogeneous gastric neuroendocrine carcinoma (G-NEC). This study analyzed the influence of surgical treatments on prognosis to provide a personalized surgical treatment strategy for G-NEC patients.

Methods

The clinicopathological data of 964 G-NEC patients from 24 Chinese hospitals were analyzed. Cox regression analyses were used to analyze the prognostic factors affecting survival and recurrence, respectively.

Results

Cox analysis revealed that in stage I-II but not stage III gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma (NEC/MANEC) patients, D2 (extended) lymph node dissection (ELND) was an independent protective factor for OS and DFS (p<0.05; p<0.05). In stage I-II, 3-year OS and DFS increased with more of LNs dissected (p<0.05), while in stage III patients undergoing ELND, the 3-year OS and DFS was similar to patients undergoing D1+ (limited) lymph node dissection (LLND) (p>0.05). Furthermore, among patients with stage III disease, the incidence of complications after ELND was significantly greater than that after LLND (28.4% vs. 12.1%, p < 0.001), especially severe complications (Clavien-Dindo grade III-V). For patients with stage I-II disease, ELLN not only brings lower overall recurrence rate (ELND vs. LLND = 16.9% vs 27.6%, p = 0.018) but also reduced the risk of regional LN and distant LN recurrence (all p < 0.05).

Conclusions

ELND may lead to enhanced long-term survival for stage I and II but not stage III NEC/MANEC patients. Our results in multicenter patients do not support the routine use of ELND in stage III NEC/MANEC patients.

Legal entity responsible for the study

The authors.

Funding

Scientific and Technological Innovation Joint Capital Projects of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

188P - The impact of sarcopenia on chemotherapy toxicity and survival rate among pancreatic cancer patients who underwent chemotherapy: A systematic review and meta-analysis (ID 235)

Presentation Number
188P
Lecture Time
09:00 - 09:00
Speakers
  • Billy Susanto (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pancreatic cancer (PC) is the most lethal cancer. Pancreatic cancer patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. The aim of this study was to study the impact of sarcopenia on chemotherapy toxicity and survival among pancreatic cancer patients who underwent chemotherapy.

Methods

A systematic review and meta-analysis was performed according to PRISMA guidelines. A literature search was conducted by two independent reviewers on all studies that included sarcopenia in hepatocellular carcinoma patients who underwent chemotherapy using PubMed, PubMed central, and Google Scholar databases. Study included elderly population was excluded. Outcome of interest included chemotherapy toxicity and overall survival. Data synthesis and statistical analysis were carried out using Review Manager software.

Results

A total of 11 studies were eligible for meta-analysis including a total of 1274 pancreatic cancer patients. All included studies were observational studies. Meta-analysis revealed a significant association between sarcopenia and overall survival (HR 1.42; 95% CI 1.20 – 1.68; P < 0.001). Sarcopenia was also associated with incidence of chemotherapy toxicity (OR 2.54; 95% CI 1.19 – 5.43; P = 0.02), including neutropenia, anemia, and thrombocytopenia. The quality of study assessed with Newcastle Ottawa Scale (NOS) showed “good” quality in all included studies.

Conclusions

Sarcopenia can give negative impact on chemotherapy toxicities and survival outcomes for pancreatic cancer patients who underwent chemotherapy. Therefore, it is important to diagnose and treat sarcopenia to reduce the chemotherapy toxicity and mortality in pancreatic cancer patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

189P - Prognostic value of inflammation-based score for patients treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) (ID 823)

Presentation Number
189P
Lecture Time
09:00 - 09:00
Speakers
  • Takahiro Yamamura (Sapporo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Inflammation-based score such as Glasgow prognostic score (GPS) or Neutrophil -Lymphocyte ratio (NLR) is associated with clinical outcome of cancer patients. However, the prognostic value of GPS and NLR for patients with advanced pancreatic cancer who received systemic chemotherapy remains unclear.

Methods

We conducted single center retrospective study. Inclusion criteria was defined as patients with metastatic or recurrent pancreatic cancer treated with FFX or GnP as first line treatment at Hokkaido university hospital between January 2014 and December 2018. Baseline GPS was identified that GPS 0 was CRP ≤1.0 mg/dL and Alb ≥3.5 g/dL, GPS 1 was CRP >1.0 mg/dL or Alb <3.5 g/dL, and GPS 2 was CRP >1.0 mg/dL and Alb <3.5 g/dL. NLR was defined as the ratio of absolute neutrophil count and absolute lymphocyte count. As no clear NLR cutoff level has been established in this setting, we used the cutoff ≧3. Cox-proportional hazards model were used to identify prognostic factors in univariate and multivariate analyses.

Results

A total of 101 patients were eligible. Median age of patients was 67, male/female was 63/38, ECOG PS 0/1/2 was 36/62/3, FFX/GnP was 19/82, GPS 0/1/2/unknown was 52/21/23/5, NLR ≧3/<3/unknown was 51/44/6, respectively. In GPS 0/1-2 patients, median PFS were 5.2/2.3months (HR 1.772, 95%CI 1.165-2.693, p=0.007), median OS were 12.4/5.7 months (HR 2.384, 95%CI 1.534-3.706, p<0.001), respectively. In NLR 3</≧3 patients, median PFS were 6.4/2.6 months (HR 2.436, 95%C.I. 1.568-3.784, p<0.001), median OS were 14.6/6.0 months (HR 2.496, 95% C.I. 1.616-3.856, p<0.001), respectively. In multivariate analysis, High NLR (NLR ≧3 vs <3 : HR 2.067, 95%C.I. 1.278-3.343, p=0.003) was significantly associated with poor PFS. For OS, female (HR 2.006, 95%C.I. 1.206-3.34, p=0.007), liver metastasis (HR 2.137, 95%C.I. 1.281-3.565, p=0.004), high NLR (NLR ≧3 vs <3: HR 2.745, 95%C.I. 1.639-4.599, p<0.001), high GPS (GPS 0 vs 1-2: HR 2.016, 95%C.I. 1.233-3.296, p<0.001) were significantly associated with poor OS.

Conclusions

NLR may be better prognosticator than GPS for patients with metastatic or recurrent pancreatic cancer treated with FFX or GnP.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Nakatsumi: Honoraria (self): Takeda; Honoraria (self): Sanofi; Honoraria (self): Merck Biopharma; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Ono Pharmaceutical. Y. Kawamoto: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Takeda; Honoraria (self): Chudai Pharma; Honoraria (self): Daiichi Sankyo; Honoraria (self): Merck; Honoraria (self): Lilly; Honoraria (self): Japan Agency for Medical Research and Development. S. Yuki: Honoraria (self): Takeda Pharmaceutical Co., Ltd.; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Sanofi K.K.; Honoraria (self): Bayer Yakuin., Ltd.; Honoraria (self): Eli Lilly K.K.; Honoraria (self): Bristol-Myers Squibb Co., Ltd.; Honoraria (self): Merck Biopharma Co., Ltd.; Honoraria (self): Chudai Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): Yakult Honsha Co., Ltd.; Honoraria (self): MSD K.K. N. Sakamoto: Honoraria (self): Gilead Sciences; Honoraria (self): Chudai Pharm; Honoraria (self): Bayer AG; Honoraria (self): Otsuka Pharm; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Astellas Pharma; Honoraria (self): Takeda; Honoraria (self): Eisai; Research grant/Funding (self): Gilead Sciences; Research grant/Funding (self): Eisai; Research grant/Funding (self): MSD; Research grant/Funding (self): Otsuka Pharm; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Asuka Pharm. Y. Komatsu: Research grant/Funding (institution): Eisai; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Yakult; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Taiho; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): MSD; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Nipro; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Asahikasei; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Nihonkayaku; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self): Kyowa Kirin; Honoraria (self): Merck Biopharma; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Shire Japan; Honoraria (self): Novartis Pharma; Honoraria (self): Pfizer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

190P - Outcomes from the Asian region of the phase III APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) alone for patients (pts) with resected pancreatic cancer (PC) (ID 205)

Presentation Number
190P
Lecture Time
09:00 - 09:00
Speakers
  • Joon Oh Park (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

APACT was a geographically diverse trial with study sites worldwide, including in Asia; here, we report outcomes from Asian sites.

Methods

Treatment-naive pts with histologically confirmed PC, R0/R1 resection, CA 19-9 < 100 U/mL, and ECOG PS ≤ 1 received 6 cycles of nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, and 15. Stratification factors were resection (R0/R1) and lymph node (LN+/−) status. The primary endpoint was disease-free survival (DFS) by independent review. Secondary endpoints were overall survival (OS) and safety.

Results

At Asian sites (Hong Kong, Korea, Singapore, and Taiwan), 108 pts (of 866 pts from the ITT population) were randomized to nab-P/G (n = 55) or G (n = 53). Median age was 61 years. Most pts had ECOG PS 0 (64%), LN+ disease (61%), and R0 resection (86%). Six treatment cycles were administered in 76% (nab-P/G) vs 77% (G) of pts. Data cutoff was April 3, 2020; median follow-up for OS was 52.6 months. Median independently assessed DFS was 27.6 (nab-P/G) vs 22.6 (G) months (Table); investigator-assessed DFS was 18.0 vs 11.9 months. Median OS was 46.8 (nab-P/G) vs 40.6 (G) months. Analgesics (nab-P/G) and treatments for indigestion (G) were the most common concomitant medications. The most common grade ≥ 3 hematologic and nonhematologic treatment-emergent adverse events (AEs) with nab-P/G vs G were neutropenia (36.4% vs 26.9%) and peripheral neuropathy (10.9% vs 0%). All dose reductions (36 [nab-P/G] vs 21 [G]) were due to AEs (most common, neutropenia); 4 (nab-P/G) vs 0 (G) pts discontinued treatment due to AEs

Outcome nab-P/G G HR (95% CI) P Value
n/N Median (95% CI), months n/N Median (95% CI), months
Asian populationa
Ind. DFS 21/55 27.6 (16.36-NA) 24/53 22.6 (10.84-NA) 0.73 (0.405-1.331)
Inv. DFS 34/55 18.0 (11.96-27.63) 35/53 11.9 (8.28-21.88) 0.73 (0.453-1.178)
OSb 30/ 55 46.8 (27.01-NA) 32/53 40.6 (24.21-48.03) 0.85 (0.513-1.398)
ITT population
Ind. DFS 226/ 432 19.4 (16.62-21.91) 213/ 434 18.8 (13.83-20.30) 0.88 (0.729-1.063) .1824
Inv. DFS 282/ 432 16.6 (14.55-19.29) 289/434 13.7 (11.24-16.00) 0.82 (0.694-0.965) .0168
OSb 248/432 41.8 (35.55-47.28) 263/434 37.7 (31.11-40.51) 0.82 (0.687-0.973) .0232

a Pts were from sites in Hong Kong (n = 4), Republic of Korea (n = 51), Singapore (n = 6), and Taiwan (n = 47). b Based on an April 3, 2020 data cutoff.CI, confidence interval; G, gemcitabine; HR, hazard ratio; Ind. DFS, disease-free survival by independent radiological review; Inv. DFS, disease-free survival by investigator review; ITT, intention-to-treat; NA, not achieved; nab-P, nab-paclitaxel; OS, overall survival.

.

Conclusions

Consistent with outcomes in the ITT population, DFS and OS were numerically longer with nab-P/G vs G in the Asian cohort. The nab-P/G safety profile was consistent with that seen in the overall treated population.

Clinical trial identification

2013-003398-91; NCT01964430.

Editorial acknowledgement

Writing assistance was provided by Mohan Harihar, of MediTech Media, Ltd., and funded by Bristol-Myers Squibb Company. The authors are fully responsible for all content and editorial decisions for this manuscript.

Legal entity responsible for the study

Bristol-Myers Squibb Company.

Funding

Bristol-Myers Squibb Company.

Disclosure

J. Bendell: Research grant/Funding (institution): Gilead, Genentech-Roche, Bristol-Myers Squibb, Five Prime, Eli Lilly & Co., Merck, MedImmune, Celgene, EMD Serono, Taiho, Macrogenics, GlaxoSmithKline, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Kol; Advisory/Consultancy: Gilead, Genentech-Roche, Bristol-Myers Squibb, Five Prime, Eli Lilly & Co., Merck, MedImmune, Celgene, Taiho, Macrogenics, GlaxoSmithKline, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Array, Sanofi,. B. Garlipp: Research grant/Funding (self): Sirtex; Honoraria (self): Sirtex, Roche, Amgen, Pfizer, Celgene, Merck and Novartis; Advisory/Consultancy: Sirtex, Roche and Amgen; Travel/Accommodation/Expenses: Merck, Amgen, Celgene, B. Braun Travacare. M. Karthaus: Advisory/Consultancy, Travel/Accommodation/Expenses: Helsinn and Riemser. B. Lu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. D. McGovern: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. S. Banerjee: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol-Myers Squibb. M. Tempero: Research grant/Funding (self): AbbVie, AstraZeneca, Advance Medical, BioPharm Communications, Bristol-Myers Squibb, CPRIT, Eisai, Halozyme, Ignyta, Immunovia, Pharmacyclics LLC, PharmaCyte Biotech, Tocagen. D-Y. Oh: Research grant/Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

191P - First-line liposomal irinotecan + 5 fluorouracil/leucovorin + oxaliplatin in patients with pancreatic ductal adenocarcinoma: Results from a phase I/II study (ID 393)

Presentation Number
191P
Lecture Time
09:00 - 09:00
Speakers
  • Andrew Dean (Subiaco, WA, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) is approved for adults with metastatic pancreatic ductal adenocarcinoma following progression with gemcitabine-based therapy. We report results from an open-label phase I/II study (NCT02551991) of adults with untreated, unresectable, locally advanced/metastatic PDAC receiving liposomal irinotecan + 5-FU/LV + oxaliplatin (NALIRIFOX).

Methods

Eligible patients were adults with ECOG performance status (PS) ≤ 1 and adequate organ function who received NALIRIFOX (liposomal irinotecan 50 mg/m2 (free base), 5-FU 2400 mg/m2, LV 400 mg/m2, oxaliplatin 60 mg/m2) on days 1 and 15 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included progression-free survival (PFS), overall survival (OS), best overall response, overall response rate (ORR), disease control rate at 16 weeks (DCR16) and duration of response (DoR). RECIST v1.1 was assessed at screening, every 8 weeks and at treatment end.

Results

Overall, 32 patients were included (median [range] age 58.0 [39–76] years; 43.8% men; 87.5% metastatic disease; 56.3% ECOG PS 1). In total, 22 patients experienced grade ≥ 3 treatment-emergent adverse events (TEAEs): neutropenia (31.3%), febrile neutropenia (12.5%), hypokalemia (12.5%), diarrhea (9.4%), nausea (9.4%) and decreased neutrophil count (9.4%). Serious TEAEs were reported in 17 patients: nausea (9.4%) and febrile neutropenia (9.4%). TEAEs led to 3 deaths (none treatment-related), to dose adjustment in 26 and discontinuation in 8 patients. Median (95% CI) PFS and OS were 9.2 (7.69–11.96) months and 12.6 (8.74–18.69) months, respectively. One patient, with locally advanced disease, had complete response, 10 partial response, and 15 stable disease. ORR (95% CI) was 34.4 (18.6–53.2) %, DCR16 was 71.9 (53.3–86.3) % and median (95% CI) DoR was 9.4 (3.52, NE) months.

Conclusions

First-line NALIRIFOX raised no new safety signals in patients with locally advanced/metastatic PDAC; anti-tumour activity was promising. The randomized phase III NAPOLI-3 study (NCT04083235) will compare NALIRIFOX with gemcitabine + nab-paclitaxel.

Clinical trial identification

NCT02551991.

Editorial acknowledgement

Alison Chisholm of Oxford PharmaGenesis, Oxford, UK, provided medical writing and editorial support, which was sponsored by Ipsen, in accordance with Good Publication Practice guidelines.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

A. Dean: Non-remunerated activity/ies: Shire; Non-remunerated activity/ies: Specialised Therapeutics; Travel/Accommodation/Expenses: Amgen. T. Bekaii-Saab: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Genetech/Rpche; Advisory/Consultancy: Glenmark; Advisory/Consultancy: Lilly; Advisory/Consultancy: Merrimack; Advisory/Consultancy: NCCN; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Research to Practice; Advisory/Consultancy: Sirtex Medical; Advisory/Consultancy: Taiho Pharmaceutical; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Merck; Advisory/Consultancy: Polaris. P.M. Boland: Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Merck; Research grant/Funding (self): Boston Biomedical; Research grant/Funding (self): Genentech; Research grant/Funding (self): Cascadian Therapeutics; Research grant/Funding (self): Advaxis; Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self): Sirtex; Advisory/Consultancy: Merrimack. F. Dayyani: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstarZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: Foundation Medecine; Advisory/Consultancy: Genetech; Advisory/Consultancy, Speaker Bureau/Expert testimony: Natera; Advisory/Consultancy: QED Therapeutics; Speaker Bureau/Expert testimony: Deciphera Pharmaceuticals; Speaker Bureau/Expert testimony: Sirtex Medical; Spouse/Financial dependant: Roche Diagnostics. T. Macarulla Mercade: Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Tesaro; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Shire; Honoraria (self): Lilly; Honoraria (self): Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy: QDE; Advisory/Consultancy: H3B; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Incyte; Advisory/Consultancy: Servier; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genetech; Research grant/Funding (institution): Halozyme; Research grant/Funding (institution): Immonomedics. K. Mody: Research grant/Funding (institution): Agios; Research grant/Funding (institution): Senwha Biosciences; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): ArQule; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution), (NIH) award # NCI/NIH P50 CA210964: National Cancer Institute (NCI) of the National Institutes of Health; Advisory/Consultancy: Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Vicus. B. Belanger: Full/Part-time employment: Ipsen. F. Maxwell: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. Y. Moore: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. A. Thiagalingam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. T. Wang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. B. Zhang: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Ipsen. Z.A. Wainberg: Advisory/Consultancy, Research grant/Funding (institution): Five Prime Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Plexxikon; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: QED Therapeutics.

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e-Poster Display Session (ID 87) Poster Display

192P - A multicenter crossover analysis of first and second-line FOLFIRINOX or gemcitabine plus nab-paclitaxel administered to pancreatic cancer patients: Results from the NAPOLEON study (ID 581)

Presentation Number
192P
Lecture Time
09:00 - 09:00
Speakers
  • Kenta Nio (Fukuoka, Fukuoka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) are considered standard 1st-line chemotherapy (CTx) for patients with metastatic pancreatic cancer, and reports about the effects of FFX and GnP as 2nd-line CTx have been accumulating. However, compared data of two crossover sequences and those of the comparison of the crossover sequences with others are unknown.

Methods

We investigated the efficacies of the two crossover sequences using the data of the multicenter observational study conducted in patients with CTx-naive advanced or unresectable pancreatic cancer (AUPC) treated with FFX or GnP from 14 hospitals in Japan during the period from December 2013 to June 2018. Patient characteristics and clinical outcomes including overall survival (OS), time-to-first and -second progression (TTFP/TTSP) and overall response rate (ORR) were analyzed between the two crossover groups [CG] firstly. Then, the efficacies of them were compared with non-crossover groups [NCG].

Results

Of 318 AUPC patients, 118 and 200 patients received FFX and GnP as 1st-line CTx, respectively. Of these, 91 and 100 patients received 2nd-line CTx, of which 72 (79%) and 17 (17%) patients were shifted to GnP (F-to-G) and FFX (G-to-F), respectively (p<0.01). The F-to-G group comprised more patients with higher body mass index, biliary drainage, peritoneal metastasis, and maximal tumor size of 20 mm or larger at baseline. In the two crossover sequences, there was no significant difference in the median OS (11.5 vs. 16.4 months; hazard ratio [HR] 1.25; p=0.45) between the F-to-G and G-to-F groups, respectively. No significant differences in the ORR of 1st-line (p=0.12) and 2nd-line (p=0.74) were seen. The median TTFP and TTSP were also comparable between the two groups (5.7 vs. 5.0 months; HR 0.99; p=0.97, 8.8 vs. 12.2 months; HR 1.12; 95% CI 0.67-2.02; p=0.58), respectively. Then, the median OS in the CG (n=89) was not significantly longer than that in the NCG (n=99) (11.6 vs. 12.8 months; HR 1.24; p=0.19).

Conclusions

There were no significant efficacy differences between the two CGs. The OS of CG was not statistically superior to NCG in our study.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

193P - First-line liposomal irinotecan + 5 fluorouracil/leucovorin + oxaliplatin in patients with pancreatic ductal adenocarcinoma: Exploratory survival analyses by change in post treatment CA 19-9 (ID 774)

Presentation Number
193P
Lecture Time
09:00 - 09:00
Speakers
  • Andrew Dean (Subiaco, WA, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) is approved for adults with metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. First-line (1L) liposomal irinotecan + 5-FU/LV + oxaliplatin (NALIRIFOX) is being investigated in a phase I/II trial of patients with locally advanced/mPDAC (NCT02551991). Serum CA 19-9 levels are typically elevated in patients with mPDAC and post-treatment reductions in CA 19-9 levels have been associated with prolonged survival. We report the results of an exploratory survival analysis from the phase I/II trial of 1L NALIRIFOX in mPDAC for subgroups defined by post-treatment changes in CA 19-9 level.

Methods

Eligible patients were adults with ECOG performance status (PS) ≤ 1 and adequate organ function who received 1L NALIRIFOX (liposomal irinotecan 50 mg/m2 (free base), 5-FU 2400 mg/m2, LV 400 mg/m2, oxaliplatin 60 mg/m2) on days 1 and 15 of each 28-day cycle. Tumors (RECIST v1.1) and serum CA 19-9 were assessed at screening, every 8 weeks and at end of treatment. Progression-free (PFS) and overall survival (OS) were compared for subgroups defined by best change in CA 19-9 level over the first 16 weeks of treatment (≥ 20% and ≥ 50% decrease; data cut-off 26 Feb 2020).

Results

In total, 32 patients were eligible for the trial, of whom 30 had a baseline CA 19-9 measurement (median [range] 315.5 [2–127115] U/mL) and 22 had a repeat CA 19-9 measurement by Week 16 (analysis set). Overall, NALIRIFOX reduced CA 19-9 level: median (range) best change of –49.4 (–100, +376)%. Median OS and PFS were numerically higher in patients with a CA 19-9 decrease ≥ 20% by Week 16 (Table)

All N = 32 Analysis set n = 22 Analysis set, by best change in CA 19-9 by Week 16
≥ 20% decrease ≥ 50% decrease
Yes n = 14 No n = 8 Yes n = 11 No n = 11
PFS
Progressed/died,a n (%) 17 (53.1) 12 (54.5) 6 (42.9) 6 (75.0) 4 (36.4) 8 (72.7)
Median (95% CI) months 9.2 (7.69, 11.96) 9.6 (7.59, 32.30) 32.3 (7.95, 32.30) 7.6 (1.48, 9.56) 11.2 (7.95, NE) 7.6 (1.48, 32.30)
HR (95% CI) 0.13 (0.04, 0.50) 0.33 (0.09, 1.12)
OS
Died, n (%) 20 (62.5) 14 (63.6) 7 (50.0) 7 (87.5) 6 (54.6) 8 (72.7)
Median (95% CI) months 12.6 (8.74, 18.69) 12.7 (8.74, 22.54) 22.5 (12.39, NE) 8.2 (2.50, 18.69) 22.5 (11.60, 22.54) 9.2 (4.83, NE)
HR (95% CI) 0.24 (0.08, 0.75) 0.55 (0.19, 1.60)

a Patients who progressed/died after new therapy or >16 weeks after last non-progressive disease assessment were censored.

.

Conclusions

1L NALIRIFOX reduced CA 19-9 levels in patients with locally advanced/mPDAC. CA 19-9 is a potential biomarker of post-NALIRIFOX outcomes in these patients.

Clinical trial identification

NCT02551991.

Editorial acknowledgement

Alison Chisholm of Oxford PharmaGenesis, Oxford, UK, provided medical writing and editorial support, which was sponsored by Ipsen, in accordance with Good Publication Practice guidelines.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

A. Dean: Non-remunerated activity/ies: Shire; Non-remunerated activity/ies: Specialised Therapeutics; Travel/Accommodation/Expenses: Amgen. T. Bekaii-Saab: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Genetech/Roche; Advisory/Consultancy: Glenmark; Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: Merrimack; Advisory/Consultancy: NCCN; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Research to Practice; Advisory/Consultancy: Sirtex Medical; Advisory/Consultancy: Taiho Pharmaceutical. P.M. Boland: Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Advaxis; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self): Sirtex; Advisory/Consultancy: Merrimack. F. Dayyani: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bristol-Meyers Sqibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Taiho Pharmaceuticals; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: Foundation Medecine; Advisory/Consultancy: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony: Natera; Advisory/Consultancy: QED Therapetuics; Speaker Bureau/Expert testimony: Deciphera Pharmaceuticals; Speaker Bureau/Expert testimony: Sirtex Medical; Spouse/Financial dependant: Roche Diagnostics. T. Macarulla Mercade: Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Tesaro; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Shire; Honoraria (self): Lilly; Honoraria (self): Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy: QDE; Advisory/Consultancy: H3B; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Incyte; Advisory/Consultancy: Servier; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Halozyme; Research grant/Funding (institution): Immunomedics. K. Mody: Research grant/Funding (institution): Agios; Research grant/Funding (institution): Senwha Biosciences; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): ArQule; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution), award # NCI/NIH P50 CA210964: National Cancer Institute (NCI) of the National Institutes of Health; Advisory/Consultancy: Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Vicus. B. Belanger: Full/Part-time employment: Ipsen. F. Maxwell: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. Y. Moore: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. T. Wang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. B. Zhang: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Ipsen. Z.A. Wainberg: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merck; Advisory/Consultancy: Lilly; Advisory/Consultancy: QED; Advisory/Consultancy: Daiichi; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer.

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e-Poster Display Session (ID 87) Poster Display

194P - Nab-paclitaxel plus capecitabine as first-line treatment for patients with recurrence or metastatic biliary tract cancer (ID 873)

Presentation Number
194P
Lecture Time
09:00 - 09:00
Speakers
  • Jun Zhou (Shijiazhuang, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Gemcitabine-based and fluoropyrimidine-based regimens demonstrated activity in phase II trials. Nab-paclitaxel plus gemcitabine was found well tolerated and may considered as an alternative regimen to current therapeutic approaches in advanced biliary tract cancer. This trial aims to evaluate safety and efficacy of nab-paclitaxel plus capecitabine in the first-line treatment of patients with recurrence or metastatic biliary tract cancer.

Methods

Patients of histopathology or cytology confirmed recurrence or metastatic biliary tract cancer (including intrahepatic cholangiocarcinoma ICC, extrahepatic cholangiocarcinoma ECC, gallbladder carcinoma GC), with ECOG PS 0-1 and adequate major organ function, were enrolled and treated with Nab-paclitaxel (125mg/m2, d1, q14d) plus capecitabine (2g/m2,bid,d1-7; q14d) until disease progression or unacceptable toxicity. The primary endpoint was ORR. The second endpoints were PFS, OS and safety. This study was registered with Chinese Clinical Trial Registry, number ChiCTR1900025004.

Results

Data cutoff date for this analysis was May 16, 2020. We recruited 18 patients, 12 (66.7%) were males, median age was 64 years (range 35-74 years), ICC/ECC/GC/NE were 4 (22.2%) / 5 (27.8%)/ 8 (44.4 %)/1 (5.6%) respectively. The median treatment cycle was 6 cycles (range 1-9). 15 patients were evaluable for efficacy. The ORR and DCR were 26.7% and 80%. The median follow-up was 8.3 months (range 4.3-13.6 months), the median PFS was 6.2 months (95% CI 3.1-NR months) and median OS was not reached. Common AEs were: leucopenia 7 (38.9%), neurotoxicity 5 (27.8%), ALT increase 3 (16.7%), AST increase 3 (16.7%), blood bilirubin increased 1 (5.6%). Most were grade 1/2.

Conclusions

Nab-paclitaxel plus capecitabine presented a clinically meaningful efficacy and a favorable safety profile as first-line treatment for recurrence or metastatic biliary tract cancer.

Clinical trial identification

ChiCTR1900025004.

Legal entity responsible for the study

The authors.

Funding

CSPC OUYI Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

370P - Bespoke circulating tumour DNA assay for the detection of minimal residual disease in esophageal adenocarcinoma patients (ID 537)

Presentation Number
370P
Lecture Time
09:00 - 09:00
Speakers
  • Emma Ococks (Cambridge, United Kingdom)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Over half of Esophageal Adenocarcinoma (EAC) patients treated with curative intent relapse. In clinical practice risk stratification is limited to TNM staging, which highlights the need for additional methods. Circulating tumor DNA (ctDNA) following surgical resection is prognostic across different tumor types. However, the sensitivity and specificity of tumor-naive ctDNA panels are limited in the minimal residual disease (MRD) setting. Additionally, EAC is known to be a low shedding tumor type, thus, a personalized, tumor-informed approach for ctDNA analysis is ideal for MRD detection after treatment and for providing prognostic value in EAC patients.

Methods

Using the prospectively collected multi-centre UK OCCAMS dataset we identified patients (n=12) with pre- and post-surgical plasma samples (n=26). Mutational profiles derived from tumor tissue were used to design assays targeting patient-specific somatic variants (Signatera™ bespoke multiplex-PCR NGS assay). The personalized assays were used to determine the presence of ctDNA in the plasma samples of EAC patients. Additional patients are currently being processed and will be presented during the meeting.

Results

The cohort consisted of 12 patients with a median age of 62.8 (48.9 – 75.8) years, of which 83% were male and were T3 at diagnosis. All patients were treated with neoadjuvant chemotherapy, of which 2 also received radiotherapy. Minimal residual disease post-surgery was detected down to a mean variant allele frequency of 0.001%. Post-operative ctDNA analysis detected clinical relapse in 4 patients with a median lead time of 196 days giving a sensitivity and specificity of 100%.

Conclusions

In this pilot study, we showed that bespoke multiplex-PCR assays for esophageal samples achieve with high sensitivity and specificity to detect recurrence in this low shedding cancer type. This result is a vast improvement over other ctDNA assays, which show <40% EAC sensitivity. Further prospective studies are warranted to investigate the clinical utility of the bespoke ctDNA assay as a modern risk stratification tool in this cancer type.

Clinical trial identification

NA

Editorial acknowledgement

Editoral support was provided by Allyson Koyen Malashevich, Ph.D. from Natera, Inc.

Legal entity responsible for the study

The authors.

Funding

Natera Inc.

Disclosure

E. Ococks: Travel/Accommodation/Expenses: Roche. A. Ng: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. S. Dashner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. W-C. Chan: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. S. Sharma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. H-T. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. H. Sethi: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. B. Zimmermann: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. E. Smyth: Honoraria (self): Astellas; Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Merck; Honoraria (self): Zymeworks; Honoraria (self): Celgene; Honoraria (self): Five Prime; Honoraria (self): Gritstone Oncology; Honoraria (self): Servier. A. Aleshin: Advisory/Consultancy: Notable Labs; Advisory/Consultancy: Mission Bio; Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. R. Fitzgerald: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Cyted Ltd.; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Roche; Licensing/Royalties, named on patents related to Cytosponge and associated assays: Patent. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

390P - A real-world clinical study of camrelizumab in the treatment of esophageal cancer (ID 603)

Presentation Number
390P
Lecture Time
09:00 - 09:00
Speakers
  • Guoping Sun (Hefei, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Camrelizumab, a fully humanized monoclonal antibody against PD-1,has been approved in the treatment of advanced esophageal squamous carcinoma in China.The purpose of this study was to observe the efficacy and safety of Camrelizumab in the treatment of esophageal cancer in the real world.

Methods

This is an open-label,prospective,multicenter, observational study. Eligible patients (pts) who received camrelizumab had esophageal cancer; age≥18, ECOG PS of 0-2; and measurable disease.

Results

From August 1, 2019 to May 1, 2020. 100 pts were enrolled. There are 80 (80.0%) males. The median age was 65.0 yrs. The majority pts were at stage IV 74(74.0%), had prior surgery 47(47.0%) and radiotherapy 61(61.0%). Pts with ECOG PS 1-2 were 85 (85.0%). Metastases were detected in 88 (88.0%) pts, which mainly were lymphatic metastasis.Pts received first-line treatment, second-line, third-line or above, respectively were 20.0%, 31.0%, 48.0%. Before immunotherapy, only one patient was tested for PD-L1. Pts received apatinib monotherapy or in combination with chemotherapy or antiangiogenictherapy,respectively were 9.0%, 39.0%, 36.0%. There were 49 patients eligible for efficacy evaluation .9 achieved partial response, 30 had stable disease and 10 got progressive disease. Thus, the objective response rate (ORR) and disease control rate (DCR) were 18.4% and 79.6%. The incidence of AEs was 55 (55.0%) and the grade 3/4 treatment-related AEs was 3 (3.0) %. Main AEs were RCCEP (18.0%), and fatigue (17.0%), anorexia (11.0%). The grade 3/4 treatment-related AEs were RCCEP (1.0%), hypothyroidism (1.0%) and anemia(1.0%).

Conclusions

In real clinical applications, Camrelizumab is mostly used in patients with poor physical condition, metastatic and late stage, and most patients had front-line treatment.PD-L-1 detection is rarely performed in patients before medication, and most patients are treated with combination therapy of Camrelizumab.Camrelizumab is confirmed to be effective and safe in patients with esophageal cancer.Further analysis is needed to determine which factors are the positive factors in the treatment of Camrelizumab.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

195TiP - GLOW: Phase III study of first-line zolbetuximab + CAPOX versus placebo + CAPOX in Claudin18.2⁺/HER2⁻ advanced/metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ) (ID 481)

Presentation Number
195TiP
Lecture Time
09:00 - 09:00
Speakers
  • Rui-Hua Xu (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Capecitabine + oxaliplatin (CAPOX) is a standard first-line treatment for advanced gastric cancer. Claudin (CLDN)18.2 is a promising targetable biomarker. In healthy tissue, CLDN18.2, a tight junction protein, is confined to gastric mucosa (ie, cells in the pit and base regions of gastric glands). Upon malignant transformation, structural loss in G/GEJ cells may allow antibodies more access to previously unavailable CLDN18.2. Zolbetuximab, a chimeric IgG1 monoclonal antibody, specifically binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Phase II (NCT01630083) results showed prolonged survival of patients with CLDN18.2-positive (CLDN18.2+) advanced G/GEJ treated with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone.

Trial design

GLOW (NCT03653507) will enroll ∼500 adults from global sites, including China, Japan, Korea, Malaysia, and Thailand. Patients must have CLDN18.2+/human epidermal growth factor receptor 2-negative (HER2) locally advanced unresectable or metastatic G/GEJ that is radiographically evaluable per RECIST v1.1. Prior treatment with chemotherapy for advanced/metastatic G/GEJ is not permitted. Patients will be randomized 1:1 to zolbetuximab + CAPOX or placebo + CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at a loading dose of 800 mg/m2 IV on Cycle 1 Day 1 followed by 600 mg/m2 IV every 3 weeks. Central testing of tumor tissue will determine CLDN18.2 and HER2 status (if unknown); patients will be considered CLDN18.2+if ≥75% of tumor cells demonstrate moderate-to-strong membranous immunohistochemical staining. The primary endpoint is progression-free survival assessed by independent review committee. Secondary endpoints are overall survival, objective response rate, and duration of response, as well as the safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of June 30, 2020, 148 sites have been initiated.

Clinical trial identification

NCT03653507.

Editorial acknowledgement

Medical writing/editorial support was provided by Patrick Tucker, PhD, Cathy R. Winter, PhD, and Elizabeth Hermans, PhD, from OPEN Health Medical Communications, Chicago, IL.

Legal entity responsible for the study

Astellas Pharma, Inc.

Funding

Astellas Pharma, Inc.

Disclosure

R-H. Xu: Honoraria (institution): Roche; Honoraria (institution): Merck. J.A. Ajani: Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma. S-E. Al-Batran: Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Pharma; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD Sharp & Dohme; Speaker Bureau/Expert testimony: AIO gGmbH; Speaker Bureau/Expert testimony: MCI; Speaker Bureau/Expert testimony: promedicis; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung; Officer/Board of Directors: IKF Klinische Krebsforschung GmbH; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Vifor; Research grant/Funding (institution): Medac; Research grant/Funding (institution): Hospira; Research grant/Funding (institution): German Cancer Aid (Krebshilfe); Research grant/Funding (institution): German Research Foundation; Research grant/Funding (institution): Federal Ministry of Education and Research. Y-J. Bang: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck Serano; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): BeiGene; Advisory/Consultancy, Research grant/Funding (institution): GreenCross; Advisory/Consultancy: Samyang Biopharm; Advisory/Consultancy: Hanmi; Advisory/Consultancy, Research grant/Funding (institution): Genexine; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Boeringer-Ingelheim; Research grant/Funding (institution): MacroGenics. D. Catenacci: Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy: BMS; Advisory/Consultancy: Lilly; Advisory/Consultancy: Gritstone; Advisory/Consultancy: Taiho; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Daichii Sankyo. P.C. Enzinger: Advisory/Consultancy: Merck; Advisory/Consultancy: Astellas; Advisory/Consultancy: Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy: Taiho; Advisory/Consultancy: Zymeworks. D.H. Ilson: Advisory/Consultancy: Astellas Pharma. S. Kim: Travel/Accommodation/Expenses: Astellas Pharma. F. Lordick: Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Eli Lilly; Travel/Accommodation/Expenses: Elsevier; Travel/Accommodation/Expenses: Biontech GmbH; Travel/Accommodation/Expenses: Excerpta Medica; Travel/Accommodation/Expenses: Medscape; Travel/Accommodation/Expenses: E-Cancer; Travel/Accommodation/Expenses: Servier; Travel/Accommodation/Expenses: Merck Serono; Travel/Accommodation/Expenses: Merck Sharpe & Dohme; Travel/Accommodation/Expenses: Springer Nature Verlag GmbH. K. Shitara: Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Dainippon Sumitomo Pharma; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Chugai Pharm; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Medi Science; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (institution): Yakult; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Glaxo Smith Kline. E. van Cutsem: Advisory/Consultancy: Astellas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Servier; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Ipsen. A. Arozullah: Full/Part-time employment: Astellas Pharma. J.W. Park: Full/Part-time employment: Astellas Pharma. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

196TiP - Perioperative sintilimab in combination with concurrent chemoradiotherapy for patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (ID 497)

Presentation Number
196TiP
Lecture Time
09:00 - 09:00
Speakers
  • Jia Wei (Nanjing, Jiangsu Province, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Concurrent chemoradiotherapy (cCRT) is the standard therapy for locally advanced gastric and GEJ adenocarcinoma with poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved to treat ≥3 line gastric and GEJ patients (pts). PACIFIC study demonstrated significant clinical benefits of PD-1 inhibitor in addition to cCRT in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116). A study was therefore designed to explore the efficacy and safety of perioperative cCRT in combination with sintilimab for pts with locally advanced gastric cancer.

Trial design

This is a prospective, open label, multicentric phase II trial which pts with locally advanced (cT3N2-3 or cT4aN+ or cT4bNany) gastric or GEJ adenocarcinoma will receive preoperative 4 cycles sintilimab in combination with S1, nab-paclitaxel (nab-PTX) and radiotherapy (RT) and post-operative 3 cycles sintilimab with S1 and nab-PTX. Sintilimab will be administered intravenously at flat dose of 200 mg every 3 wks. S1 orally at dose of 40 mg/m2 (bid) and nab-PTX intravenously at 100-120 mg/m2 (d1, d8) will be given for 2 cycles before surgery and 3 cycles after. A weekly nab-PTX (80-100 mg/m2,d1, d8, d15, d22) with concurrent RT (45Gy/1.8Gy*25f) will be given in between 2 cycles of S1 and nab-PTX combination. The primary endpoint is the pathological complete response (pCR), and a Simon optimal two-stage design will be employed to achieve the target at 35% from historical 15%. Secondary endpoints include safety, major pathological response (MPR) (defined by tumor residual ≤10%), R0 resection rate, and overall survival. Collateral translational studies explore the correlation of response with tumor mutational burden or genetic alterations, or biomarkers etc. The trial is now open to enrollment, 13 of planned 34 pts have been enrolled.

Clinical trial identification

ChiCTR1900024428.

Legal entity responsible for the study

Affiliated Drum Tower Hospital to Medical School of Nanjing University.

Funding

Innovent Biologics.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

197TiP - A randomized, double-blind, phase III study of pembrolizumab plus chemotherapy as first-line therapy in patients with HER2-negative, advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: KEYNOTE-859 (ID 1010)

Presentation Number
197TiP
Lecture Time
09:00 - 09:00
Speakers
  • Shukui Qin (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For patients with HER2–negative recurrent or metastatic G/GEJ cancer, standard first-line therapy includes a fluoropyrimidine + a platinum-based agent. Accumulating evidence has shown that PD-1 inhibitor pembrolizumab + chemotherapy can improve clinical outcomes in this population. The phase III KEYNOTE-859 trial (NCT03675737) is investigating first-line pembrolizumab + chemotherapy in patients with advanced G/GEJ cancer.

Trial design

Eligible patients are ≥18 years old with previously untreated HER2–negative advanced G/GEJ adenocarcinoma, measurable disease per RECIST v1.1, adequate tumor tissue sample for PD-L1 biomarker analysis, and ECOG performance status 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously (IV) every 3 weeks (Q3W) in combination with the investigator’s choice of FP (continuous infusion of 5-fluorouracil [800 mg/m2/day on days 1-5 of each cycle] + IV cisplatin [80 mg/m2] Q3W) or CAPOX (oral capecitabine [1000 mg/m2 twice daily on days 1-14 of each cycle] + IV oxaliplatin [130 mg/m2 on day 1 of each cycle] Q3W). Duration of cisplatin or oxaliplatin may be capped at 6 cycles per local country guidelines; treatment with 5-fluorouracil or capecitabine may continue per protocol. Treatment with pembrolizumab/placebo will continue for up to 35 administrations (∼2 years) or until disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, or noncompliance. Patients will be stratified by geographic region (Europe/Israel/North America/Australia vs Asia vs rest of world), PD-L1 tumor expression status (combined positive score <1 vs ≥1), and combination chemotherapy (FP vs CAPOX). Imaging will be performed Q6W, and adverse events (AEs) will be monitored throughout the study and for 30 days after treatment (90 days for serious AEs). The dual primary end points are OS and PFS per RECIST v1.1 as assessed by blinded independent central review (BICR). Secondary end points include ORR and DOR per RECIST v1.1 as assessed by BICR and safety. Enrollment is ongoing.

Clinical trial identification

NCT03675737.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Holly C. Cappelli, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Funding for this study was provided by Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Tabernero: Advisory/Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. E. van Cutsem: Advisory/Consultancy: Bayer, Lilly, Roche, Servier, BMS, Celegene, MSD, Merck KGaA, Novartis, AstraZeneca, Halozyme, Array BioPharma; Research grant/Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Lilly, Novartis, Roche, Celegene, Ipsen, Merck, Merck KGaA, Servier, BMS. C.S. Fuchs: Advisory/Consultancy: Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, Evolveimmune Therapeutics, Genentech, Merck, Taiho, Unum Therapeutics; Leadership role: CytomX Therapeutics (director), Evolveimmune Therapeutics (co-founder); Shareholder/Stockholder/Stock options: CytomX Therapeutics and Entrinsic Health excised options; Evolveimmune Therapeutics. Y.Y. Janjigian: Advisory/Consultancy: Lilly, Pfizer, Merck, Bristol-Myers Squibb, Merck Serono; Research grant/Funding (self): Boehringer Ingelheim, Bayer, Lilly, Amgen, Roche, Genentech. P. Bhagia: Full/Part-time employment: Merck & Co., Inc. K. Li: Full/Part-time employment: Merck & Co., Inc. D. Adelberg: Full/Part-time employment: Merck & Co., Inc. Y-J. Bang: Advisory/Consultancy: AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serano, Bayer, BMS, Eli Lilly, Taiho, Daiich-Sankyo, Astellas, BeiGene, GreenCross, Samyang Biopharm, Hanmi, Genexine; Research grant/Funding (institution): AstraZeneca, Novartis, Genentech/Roche, MSD, Merck Serano, Bayer, BMS, GSK, Pfizer, Eli Lilly, Boeringer-Ingelheim, MacroGenics, Boston Biomedical, FivePrime, Curis, Taiho, Takeda, Ono, Daiichi Sankyo, Astellas, BeiGene, Green Cross, CKD Pharma, Genexi. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

198TiP - SPOTLIGHT: Phase III study of zolbetuximab + mFOLFOX6 versus placebo + mFOLFOX6 in first-line Claudin18.2⁺/HER2⁻ advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ) (ID 634)

Presentation Number
198TiP
Lecture Time
09:00 - 09:00
Speakers
  • Kohei Shitara (Kashiwa, Chiba, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Fluorouracil, folinic acid, and oxaliplatin (mFOLFOX6) is accepted first-line therapy for advanced/metastatic G/GEJ. Claudin (CLDN)18.2, a tight junction protein and new molecular target, is confined to gastric mucosa (ie, cells in the pit and base regions of the gastric glands) in healthy tissue. Upon malignant transformation, structural loss in G/GEJ cells may allow antibodies more access to previously unavailable CLDN18.2. Zolbetuximab (zolbe), a chimeric IgG1 monoclonal antibody, binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Phase II (NCT01630083) results showed prolonged survival of patients (pts) with CLDN18.2+ advanced G/GEJ treated with zolbe + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone.

Trial design

SPOTLIGHT (NCT03504397) is enrolling ∼550 pts from global sites including China, Japan, Korea, and Taiwan. Eligible pts should have locally advanced unresectable or metastatic G/GEJ that is CLDN18.2+/human epidermal growth factor receptor 2-negative (HER2) and radiologically evaluable lesions per RECIST v1.1. Prior chemotherapy for advanced/metastatic G/GEJ is not permitted. Patients will be randomized 1:1 to zolbe + mFOLFOX6 or placebo + mFOLFOX6. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Patients will receive zolbe 800 mg/m2 IV on Cycle 1 Day 1 (loading dose), then 600 mg/m2 IV every 3 weeks; mFOLFOX6 will be administered on Days 1, 15, and 29 of each 42-day cycle (4 cycles). Central tumor tissue testing will determine CLDN18.2/HER2 status (if unknown); pts are considered CLDN18.2+ if ≥75% of tumor cells show moderate-to-strong immunohistochemical staining. Primary endpoint: progression-free survival per independent review committee. Key secondary endpoint: overall survival. Other secondary endpoints: objective response rate; duration of response; safety/tolerability, pharmacokinetics, and immunogenicity of zolbe. As of June 30, 2020, 190 sites have been initiated.

Clinical trial identification

NCT03504397.

Editorial acknowledgement

Medical writing/editorial support was provided by Patrick Tucker, PhD, Cathy R. Winter, PhD, and Elizabeth Hermans, PhD, from OPEN Health Medical Communications, Chicago, IL.

Legal entity responsible for the study

Astellas Pharma, Inc.

Funding

This study was funded by Astellas Pharma, Inc.

Disclosure

K. Shitara: Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Dainippon Sumitomo Pharma; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Chugai Pharm; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Medi Science; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (institution): Yakult; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy: GlaxoSmithKline. S-E. Al-Batran: Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Pharma; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD Sharp & Dohme; Speaker Bureau/Expert testimony: AIO gGmbH; Speaker Bureau/Expert testimony: MCI; Speaker Bureau/Expert testimony: promedicis; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung; Officer/Board of Directors: IKF Klinische Krebsforschung GmbH; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Vifor; Research grant/Funding (institution): Medac; Research grant/Funding (institution): Hospira; Research grant/Funding (institution): German Cancer Aid (Krebshilfe); Research grant/Funding (institution): German Research Foundation; Research grant/Funding (institution): Federal Ministry of Education and Research. Y-J. Bang: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck Serano; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): BeiGene; Advisory/Consultancy, Research grant/Funding (institution): GreenCross; Advisory/Consultancy: Samyang Biopharm; Advisory/Consultancy: Hanmi; Advisory/Consultancy, Research grant/Funding (institution): Genexine; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Boeringer Ingelheim; Research grant/Funding (institution): MacroGenics. D. Catenacci: Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy: BMS; Advisory/Consultancy: Lilly; Advisory/Consultancy: Gritstone; Advisory/Consultancy: Taiho; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Daichii Sankyo. P.C. Enzinger: Advisory/Consultancy: Merck; Advisory/Consultancy: Astellas; Advisory/Consultancy: Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: Loxo; Advisory/Consultancy: Taiho; Advisory/Consultancy: Zymeworks. D.H. Ilson: Advisory/Consultancy: Astellas Pharma. S. Kim: Travel/Accommodation/Expenses: Astellas Pharma. F. Lordick: Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol Myers Squibb; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Eli Lilly; Travel/Accommodation/Expenses: Elsevier; Travel/Accommodation/Expenses: Biontech GmbH; Travel/Accommodation/Expenses: Excerpta Medica; Travel/Accommodation/Expenses: Medscape; Travel/Accommodation/Expenses: E-Cancer; Travel/Accommodation/Expenses: Servier; Travel/Accommodation/Expenses: Merck Serono; Travel/Accommodation/Expenses: Merck Sharpe Dohme; Travel/Accommodation/Expenses: Springer Nature Verlag GmbH. E. van Cutsem: Advisory/Consultancy: Astellas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Servier; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Ipsen. R-H. Xu: Honoraria (institution): Merck; Honoraria (institution): Roche. A. Arozullah: Full/Part-time employment: Astellas Pharma. J.W. Park: Full/Part-time employment: Astellas Pharma. J.A. Ajani: Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO8 - A ‘Trojan Horse’ kidney transplant: uncommon metastasis from organ donation (ID 517)

Presentation Number
YO8
Lecture Time
09:00 - 09:00
Speakers
  • Marcelle G. Cesca (Sao Paulo, Brazil)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

Background: The risk of developing primary tumors succeeding organ transplantation is significant. The transmission of cancer from organ donation, however, is rare, with sporadic cases being reported. In these scenarios, the common features are primary cancers in the transplanted organs or metastasis from tumors with high propensity to spread to these organs.

Case report: We report a case of a black female patient, 30 years old, who had Mayer-Rokitansky-Küster-Hauser syndrome and chronic kidney disease, resulting from multiple urinary tract infections. In July 2016, after five years of hemodialysis, she underwent a kidney transplant from a deceased donor. In March 2017, a biopsy of the transplanted kidney was done, due to renal failure. The biopsy suggested a poorly differentiated carcinoma, with probable pancreatobiliary origin (Immunohistochemistry: AE1/AE3, CK7, CDX2, 34bE12 positive and CK20, TTF1, estrogen receptor, p63, BRST negative). Extrarenal disease was not found by staging images. On April 24th, 2017, nephroureterectomy and lymphadenectomy were performed, with the pathology confirming pancreatobiliary carcinoma. She returned to hemodialysis sessions. After 6 months of surveillance, local recurrence as a mass in the right iliac fossa was detected. Following three cycles of carboplatin + gemcitabine, a complete metabolic response was observed in PET scan and chemotherapy was stopped due to hematologic toxicity. Currently, the patient is still under surveillance, with no evidence of invasive disease. Considering the time elapsed from organ transplantation and cancer development in this report, it is expected that the neoplasm was transmitted from the donor. Most of these cases have deceased donors. In the absence of a macroscopic primary tumor, it is difficult to hypothesize that there was contiguous invasion. Despite of the rarity of renal metastasis from primary pancreatobiliary cancers, we considered this justification for the case.

Conclusion: This is a case report of cancer transmission from kidney transplant, with uncommon metastasis site from the suggested primary tumor. Considering the unfeasibility to prospective trials and the rarity of these cases, this kind of reports are crucial.

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e-Poster Display Session (ID 87) Poster Display

YO9 - Prolonged survival of HER2-positive proximal esophageal adenocarcinoma (ID 652)

Presentation Number
YO9
Lecture Time
09:00 - 09:00
Speakers
  • Erick F. Saldanha (Sao Paulo, Brazil)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

Esophageal adenocarcinoma (EAC) is a poor prognostic disease, the 5-year survival rate for people with esophageal cancer is 20%. According to the current literature, the rate of HER2 positivity in EAC varies, ranging from 15 to 29%. Currently there is no data about the incidence rates of HER2-positive proximal EAC.

76-year old man presented in 2015 to our hospital, ECOG 1, with loss of weight and dysphagia. His Medical history was significant for primary hypertension and benign prostate hyperplasia. He was an active Smoker (30 pack-years) and Alcoholic. Denied family history for neoplasm.

Initial staging with upper gastroinstestinal (UGI) endoscopy shows a circumferential, friable, ulcerated and infiltrative lesion that is 19 cm from the ADS and extends up to 26 cm. CT showed thickening of the middle and proximal esophagus with regional lymph node enlargement. Presence of distant metastases was not detected.

Histopathological findings showed Proximal esophagus moderately differentiated, ulcerated and invasive adenocarcinoma. Immunohistochemical (IHC) analysis showed HER2 3+, CK7 positive, CK20 positive, CDX2 positive and GATA-3 negative.

At the time given the lack of accurate data on anti HER2 therapy for EAC, the sistemic chemotherapy (CT) chosen was carboplatin plus Paclitaxel. After 5 months he presented local progression. We chose Folfox as next line CT and after that local Radiotherapy. Follow up with CT Scans and UGI endoscopy.

After 4 years of stable disease patient presented to our hospital with odinophagy, increased esophageal lesion and loss of weight. we proposed modified FOLFOX (mFOLFOX) with dose reduction 5-FU and oxaliplatin. After 2 cycles of mFOLFOX the patient is currently presenting good clinical response.

Overexpression and amplification of HER2 is generally correlated with worse prognosis in solid malignancies. The impact of HER2 overexpression on EAC are conflicting, since studies do not differ EAC from gastric cancer and esophageal.

Recent studies shows negative results with adding Trastuzumab to standard of care. Despite that HER 2 remains an important target. Precision oncology is currently working on trials to access different ways to access these biomarkers.

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e-Poster Display Session (ID 87) Poster Display

YO10 - Intra-arterial chemotherapy as induction for metastasectomy in gastric cancer (ID 655)

Presentation Number
YO10
Lecture Time
09:00 - 09:00
Speakers
  • Francisca G. Moura (Sao Paulo, Brazil)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

We report a case of a 32-year-old Brazilian male, asymptomatic, who underwent an esophagogastroduodenoscopy in July 2014, which revealed a friable exophytic lesion in the esophagogastric junction (EGJ), Siewert 1. The biopsy of the lesion showed a well-differentiated intestinal-type adenocarcinoma, HER2 negative. The patient received neoadjuvant chemoradiotherapy with Carboplatin and Paclitaxel, followed by a distal esophagectomy and gastrectomy with extended D2 lymph node dissection. A partial pathological response (ypT2pN0) was obtained. Surveillance was initiated. In May 2016, a Computerized Tomography (CT) revealed suspicious hepatic nodules, which were confirmed as metastasis from gastric cancer by liver biopsy. He underwent first-line chemotherapy with mFOLFOX6, but the oxaliplatin was suspended after twelve cycles due to limiting peripheral neuropathy. There was observed hepatic disease progression after twenty four cycles with 5-Fluoracil .The treatment was then modified to FOLFIRI, resulting in progressive disease after 4 cycles. Due to limitations stemming from the public healthcare service and to prior toxicity, a decision to employ mFOLFOX6 intra-arterial infusion was made. The patient had a good response to the treatment, with no significant toxicity. In July 2018, a hepatic embolization was performed, followed by hepatic segmentectomy (segments VI, VII and VIII). At two years’ follow-up, the patient is alive and with no evidence of recurrence.

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e-Poster Display Session (ID 87) Poster Display

YO11 - necrotizing fasciitis at limbs after peritoneal chemotherapy in a gastric cancer pantient (ID 761)

Presentation Number
YO11
Lecture Time
09:00 - 09:00
Speakers
  • Junwei Wu (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

A 65-yr women presented in 12/2018 with fecal OB+ and anemia. Endoscopy showed esophageal-gastric body invasive lesion. Biopsy verified low differentiate carcinoma, Her-2(0). PET-CT showed multiple lymph nodes,mesenteric, omental metastasis. She was treated with chemotherapy(paclitaxel+S1). During the chemo,red plaques like rash appeared on hands and face.Dermatologist considered dermatitis medicamentosa and treated with Tacrolimus.The rash subsided but leaved the pigmentation.The efficacy of chemo reached PR.On 23/8/2019,she received laparoscopic exploration and radical total gastrectomy(ypT4aN3M0,IIIC). In 3/2020,CT scan showed double pyeloectasis and low biliarty obstruction caused by recurrent peritoneal metastasis. After the pyelostomy and PTCD,her renal and liver function recovered.MFOLFOX7 was tried to control the tumor progression. However,ascites appeared and some adenocarcinoma cells were found among exfoliated cells of the ascites.

On 16/5/2020, after the drainage of ascites, 60mg paclitaxel was treated as intraperitoneal infusion chemotherapy. On 17/5/2020, red plague rashes appeared at hands and feet. A day later,blisters appeared and extremities of limbs turned to blackened.Besides skin change, the patient had hypotension,fever and diarrhea. Dermatologist diagnosed it as fixed drug eruption since the history of dermatitis medicamentosa. Glucocorticoids for external and intravenous use was recommended. However the lesion of the skin continued to progressed fast. The gangrene of the extremities was worsen on 19/5/2020. The limb doppler US did not discovered any thrombus at main arteries. The second dermatological consultation diagnosis was necrotizing fasciitis.Moreover PCT evaluated >200ng/ml,CRP was 166ng/L. Blood cell decreased thoroughly,which indicated hemophagocytic syndrome caused by serious infection. Since the patient suffered the septicopyemia combined with metastatic gastric cancer, prognosis was poor. Intensive therapy was given up. On 20/5/2020, the patient passed away. After her death,the bacterial culture of the blister fluid abtained when she was alive, came out to be the aeromonas hydrophil,which may cause the necrotizing fasciitis.

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e-Poster Display Session (ID 87) Poster Display

Genitourinary tumours, non-prostate (ID 1147)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

204P - Prospective observational study on pazopanib in patients treated for advanced or metastatic renal cell carcinoma (RCC) in Asia, North Africa and Middle East countries: Final analysis of PARACHUTE study (ID 443)

Presentation Number
204P
Lecture Time
09:00 - 09:00
Speakers
  • Ravindran Kanesvaran (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

PARACHUTE, a phase IV, observational study of treatment patterns and outcomes planned to describe the clinical effectiveness and safety of pazopanib in patients (pts) with advanced or mRCC who are naïve to VEGF-TKI therapy in the real-life setting from Asia Pacific, North Africa, and the Middle East countries where data from the registration trials are lacking.

Methods

Eligible pts were ≥18y with advanced or mRCC and clinical decision to initiate pazopanib treatment or had already started new treatment with pazopanib within 15 days prior to study entry and naïve to any prior anti-VEGF therapy. Primary endpoint was the proportion of pts remaining progression free at 12 months (mo). The secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).

Results

Between Jun 2017 and Dec 2018, 200 pts were enrolled from 15 countries in Asia, North Africa and Middle East. A total of 190 pts with a median age of 61y (range, 22.0-96.0) were included in this final analysis. Majority of the pts were Asian (70%), clear-cell type RCC was the most common (80%), with a favourable (9%), intermediate (47%), poor (10%) and unknown (34%) MSKCC risk score. At end of observation period, 78 pts completed the observational period and 112 discontinued the study. 60% of pts had the starting dose at 800mg. Median RDI was 82% with 52% pts received <85%. 56 of 145 evaluable pts (39%) remained progression-free at 12 mo and median PFS was 10 mo (95% CI, 8.48-11.83). 19% of pts (21/109) were long-term responders (on pazopanib for ≥18mo). The best ORR per RECIST 1.1 was CR/PR in 24%, SD in 44% and PD in 31%. The major reason for switching to other treatment was disease progression with 86%. 73% pts reported ≥1 treatment related adverse event (TRAE). Most frequent (>10%) TRAEs include, diarrhea (30%), palmar-plantar erythrodysaesthesia syndrome (15%) and hypertension (14%).

Conclusions

The final analysis results of the PARACHUTE study support the use of pazopanib in pts with advanced or mRCC who are naïve to VEGF-TKI therapy. The safety profile is consistent with the previously reported pivotal and real-world evidence studies.

Editorial acknowledgement

Medical writing and editorial support was provided by Anuradha Bandaru, Novartis Healthcare Pvt Ltd (Hyderabad, India).

Legal entity responsible for the study

Novartis.

Funding

Has not received any funding.

Disclosure

R. Kanesvaran: Research grant/Funding (self): Eisai; Research grant/Funding (self): Ipsen; Research grant/Funding (self): BMS; Research grant/Funding (self): MSD; Research grant/Funding (self): Pfizer. P. Danchaivijitr: Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Pfizer. T. Hashem: Advisory/Consultancy, Speaker Bureau/Expert testimony: Hoffman-La Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen Cilag; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Advisory/Consultancy, Speaker Bureau/Expert testimony: Mundi Pharma. B. Karabulut: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sereno; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: J&J; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. C. Chikatapu: Full/Part-time employment: Novartis. S. Ingles: Full/Part-time employment: Stamford Consultants AG; Full/Part-time employment: Novartis Pharma AG; Shareholder/Stockholder/Stock options: Novartis Pharma AG. K. Silmane: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharma S.A.S. M. Erman: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Gen Ilac; Honoraria (self), Advisory/Consultancy: Nobel Ilac; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Beigene; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Lilly. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

205P - A study on organ preservation in muscle invasive urinary bladder cancer patients with intensity modulated radiotherapy and concurrent single agent cisplatin in south Indian population (ID 446)

Presentation Number
205P
Lecture Time
09:00 - 09:00
Speakers
  • Himani Manchala (Hyderabad, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The standard care for muscle invasive bladder carcinoma (MIBC) in the United States for a long time was radical cystectomy where as in Europe, it is radical radiotherapy or multidrug regimen neoadjuvant chemotherapy followed by radiotherapy. In spite of the importance in terms of incidence, prognosis and cost, bladder cancer research remains significantly underfunded so the studies and data on organ preservation in MIBC in India are less explored.

Methods

We analyzed the data of 30 patients of MIBC from 2016-2018 who underwent primary transurethral resection of bladder tumour (TURBT) followed by IMRT with 64.8 Gy and weekly cisplatin at dose of 40 mg/ m2 with median follow up of 10 months. The role of various factors like tumour stage, histopathology, grade, complete TURBT, obstructive uropathy on locoregional response and disease free survival was evaluated. Local reactions evaluated using CTCAE criteria version 5.0. Statistical analysis was done using SPSS version 23.0.

Results

Demographic and disease characteristics

Age Median – 68 Yrs Range – 52 - 80 Yrs
Sex Male – 86.7% (n=26) Female – 13.3% (n=4)
Turbt Complete – 33.3% (n=10) Incomplete – 66.7% (n=20)
Histopathology Transitional – 86.6%(n=26) Squamous – 6.7% (n=2) Adeno CA – 6.7% (n=2)
Grade Grade I – 6.7% (n=2) Grade II – 26.6% (n=8) Grade III - 66.7% (n=20)
Tumour Stage T2 – 53.3 % (n=16) T3 – 33.3 % (n=10) T4 – 13.4 % (n=4)
Obstructive Uropathy Present – 33.3 % (n=10) Absent – 66.7% (n=20)
Locoregional Response Complete – 73.3% (n=22) Partial – 20% (n=6) Progression – 6.7% (n=2)

After the treatment, the complete locoregional response (LRR) was 73.3%. Early (T2 stage) tumours (p= 0.043) and patients without obstructive uropathy (p= 0.039) have shown significant LRR. Patients with complete TURBT, Low grade tumours shown increased response though statistically not significant. The overall disease free survival in this study for the preserved bladder patients is 53.3%. Patients without obstructive uropathy have shown significant DFS of 70% (p=0.026). Improved DFS of patients with T2 stage tumours (75%), complete TURBT (60%), low grade tumours was observed though statistically not significant. GU toxicities like dysuria, burning micturition in 40% of patients, increased frequency of micturition in 20% of patients, gastro intestinal toxicities like constipation (40%), pain abdomen (6.7%) were observed during followup and all these are grade I,II and managed well with supportive treatment.

Conclusions

Bladder preservation in more than 70% of patients in this study supports the general concept of organ sparing treatment in oncology. The high response rate and DFS were observed in south Indians with complete TURBT, early stage tumours, no obstructive uropathy and low grade tumours. The genito urinary & gastro intestinal toxicities are comparatively less, probably in view of using IMRT technique and single agent cisplatin.

Legal entity responsible for the study

Dr Himani Manchala.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

206P - Mutational signature in urothelial carcinoma with TP53 mutation (ID 832)

Presentation Number
206P
Lecture Time
09:00 - 09:00
Speakers
  • Huan H. Liu (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The key roles of the TP53 mutation in cancer have been well established. However, the different biological processes of urothelial carcinoma (UC) stratified by the TP53 mutation status has not yet been described. Mutational signatures can reveal biological processes underlying carcinogenesis.

Methods

Patients diagnosed with UC were enrolled in the study. Tumor tissue and matching blood were sequenced by next-generation sequencing (NGS) techniques with Acornmed panel with 808 cancer-related genes.

Results

A total of 139 patients were enrolled including 69 patients with TP53 mutation and 70 patients with TP53 wildtype. In TP53 mutation cohorts, the five most frequently mutated genes were TP53 (100%), KMT2D (55%), RB1 (29%), KMT2C (26%), and FAT1 (25%). For TP53 wildtype cohorts, the five most frequently mutated genes were KMT2D (43%), FGFR3 (30%), FAT1 (28%), BRD4 (26%), and KMT2C (25%). For top 20 gene, 4 frequently mutated genes were significant difference between TP53 mutation and TP53 wildtype cohorts, such as ERBB3, FGFR3, ERCC2, and STAG2, excluding the TP53 gene. C to T (C>T) substitutions and transitions were dominant mutation types in both cohorts (39.8% and 44.0%, 50% and 55%, respectively). APOBEC Cytidine Deaminase (Signature 2) were shown in both cohorts. Surprising, exposure to aristolochic acid (Signature 22) and defective DNA mismatch repair (Signature 6) were only existed in TP53 mutation cohorts, whereas spontaneous deamination of 5−methylcytosine (Signature 1) and defects in polymerase POLE (Signature 10) were only discovered in TP53 wildtype cohorts.

Conclusions

There were characterized the genomic differences and similarities, stratified by the TP53 status, which may reflect the UC patients with TP53 mutation harbored a specific biological process.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H.H. Liu, X.Y. Liang, L.B. Chen, Y. Zhang, H.N. Wang, F. Lou, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd.

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e-Poster Display Session (ID 87) Poster Display

208P - Prognostic factors and outcomes of non-seminomatous germ cell tumours of testis: Experience from a tertiary cancer centre in India (ID 952)

Presentation Number
208P
Lecture Time
09:00 - 09:00
Speakers
  • Lekha M. Nair (Thiruvananthapuram, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Germ cell tumours of testis is the most common cancer in young men in the western world. India has the lowest incidence globally and hence Indian data is sparse. We report the outcomes of patients with non-seminomatous germ cell tumours of testis treated at a tertiary cancer centre in South India over a period of ten years.

Methods

Patients with a histopathological diagnosis of non-seminomatous germ cell tumours of testis from Jan 1, 2006 to Dec 31, 2016 were included in the study. Patient demographics, tumour characteristics and treatment details were retrieved from case records. Kaplan-Meier method was used to estimate progression-free survival and overall survival. Cox regression model was used to analyse the prognostic factors.

Results

One hundred and nineteen patients with non-seminomatous germ cell tumours of testis of testis were included in the study. The median follow-up was 81 months. The estimated four-year overall survival and progression-free survival was 87.1% and 84.5% respectively. The four-year overall survival for good, intermediate and poor-risk groups was 93.6%,87.5% and for 52.6% respectively. The progression-free survival at four years was 91.4%, 87.8% and 47.4% for good, intermediate and poor-risk groups respectively. The presence of non-pulmonary visceral metastasis and biochemical response after chemotherapy were significant factors for overall survival and progression free survival in multivariate cox proportional hazards regression.

Conclusions

The survival figures are comparable to the rest of the world except in the poor prognostic risk group. The inferior survival noticed in this group of patients may be due to the lack of good salvage procedures. High dose chemotherapy with stem cell support may be considered more often for this group of patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

210P - Prognostic value of sarcopenia in metastatic renal cell carcinoma patients: A systematic review (ID 350)

Presentation Number
210P
Lecture Time
09:00 - 09:00
Speakers
  • Angeline Tancherla (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Sarcopenia is a degenerative loss of skeletal muscle mass that can be found in the development of cancer cachexia. Based on recent studies, the prevalence of sarcopenia is relatively high in mRCC (metastatic renal cell carcinoma) patients, with the rate of 29-68%. Sarcopenia has been associated with increased adverse outcomes and could be an important predictor of outcomes in some types of cancer. However, the prognostic value of sarcopenia in renal cancer patients is still unclear. Thus, in this systematic review, we aim to evaluate the prognostic value of sarcopenia in mRCC patients.

Methods

Data is collected from PMC, PubMed, Scopus, and Science Direct, using combinations of keywords related to Sarcopenia and mRCC. We included studies that investigate sarcopenia in relation to survival and primary chemotoxicity in mRCC patients. Quality of each included study is assessed using the Newcastle-Ottawa Scale (NOS).

Results

A total of 10 studies consisting of 849 mRCC patients were included. According to the NOS, there were 5 studies with good quality, 4 studies with moderate quality, and 1 study with poor quality. The association of sarcopenia and OS (Overall Survival) was found in 4 studies. However, other 5 studies showed that sarcopenia was not associated with OS. Similar results for PFS (Progression Free Survival) were found. Two studies found that sarcopenia was associated with PFS, while other 2 studies found that there was no association between sarcopenia and PFS. There were 3 studies that found a higher DLT (Dose-Limiting Toxicity) rate in sarcopenic patients vs. non sarcopenic patients treated with sunitinib and sorafenib. However, other 2 studies found that there were no significant differences in chemotherapy toxicity between sarcopenic and non-sarcopenic patients treated with tyrosine kinase inhibitor and everolimus.

Conclusions

In this systematic review, we observed that sarcopenia was associated with increased DLT and poor survival in some studies, but the results were inconsistent and conflicting. There were 5 studies with good quality, 4 studies with moderate quality, and 1 study with poor quality. Further investigation is needed with better methods and outcome that focuses on chemotherapy toxicity and quality of life.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

211P - The impact of low muscle mass to overall survival in bladder cancer patients undergoing chemotherapy: A systematic review and meta-analysis (ID 432)

Presentation Number
211P
Lecture Time
09:00 - 09:00
Speakers
  • Karunia V. Japar (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Bladder cancer belongs to one of the top ten most common cancers in the world with approximately 550,000 cases annually. The general 5-year survival rate for people with bladder cancer is 77%. The overall 10-year survival rate is 70% and the overall 15-year survival rate is 65%. Low muscle mass is prevalent in these patients receiving chemotherapy. In this meta-analysis, we aim to assess the impact of low muscle mass on overall survival in bladder cancer patients undergoing chemotherapy.

Methods

A systematic review was performed according to PRISMA guidelines. A literature search using confidence method, was conducted by two independent reviewers on all of the studies that include low muscle mass in bladder cancer patients undergoing chemotherapy using Google Scholar, PubMed, and PubMed central databases. Outcome of interest in this study is the overall survival. Data synthesis and statistical analysis were carried out using Review Manager Software.

Results

A total of 4 studies were eligible for meta-analysis including a total of 370 bladder cancer patients undergoing chemotherapy. All of the studies were observational studies. Meta-analysis revealed that there are no association between low muscle mass and overall survival (HR 1.24; 95% CI 0.71-2.19; P< 0.45). The quality of this study was assessed with Newcastle Ottawa Scale (NOS) shows “good” quality in all included studies.

Conclusions

Our meta-analysis shows that low muscle mass is not associated with the overall survival of bladder cancer patients undergoing chemotherapy. Further study need evaluate in better patient selection and adjusting the confounder.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

212P - Stage I non-seminoma testicular cancer: Adjuvant management and outcomes (ID 483)

Presentation Number
212P
Lecture Time
09:00 - 09:00
Speakers
  • Gaik Tin Quah (Newcastle, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Treatment options for stage 1 (CS1) non-seminoma testicular cancer (NSGCT) following surgery include active surveillance (AS) or adjuvant bleomycin, etoposide and cisplatin (BEP). Presence of lymphovascular invasion (LVI) and embryonal carcinoma (EC) have been associated with an increased risk of relapse.(1)

Methods

Data on CS1 testicular cancer patients presenting to two sites in Western Sydney between 1990 and 2019 were analysed. Tumour characteristics including tumour markers, size of primary, LVI, rete testis involvement (RTI) and histology were correlated with relapse.

Results

A total of 168 cases of CS1 NSGCT were identified. None of the 20 patients who received 2 cycles of adjuvant BEP relapsed, compared to 47 of 148 (32%) on AS. All relapsed patients received BEP and 19 (40%) had post-chemotherapy surgery. 14 out of 19 resection samples showed residual teratoma, and the remaining showed necrotic tumour. There were 2 deaths from relapse, and 1 from other causes. RFS at 5 years was 71% and OS 97%. In AS patients, LVI and RTI were predictors of relapse with HR of 8.50 (95% CI 4.12, 17.54, p=<.0001)) and 3.12 (95% CI 1.46, 6.70, p=0.01). 29 of 44 pts (66%) with LVI relapsed compared to 10 of 85 (12%) without LVI. EC was not associated with relapse. (HR 1.80; CI 0.71, 4.57, p=0.2).

Conclusions

In our series, relapse rate of 32% in AS group is in keeping with published data from a large population-cohort study.(1) LVI was associated with an almost 9-fold increase in risk of recurrence, also consistent with previous findings. Of those, 40% required post-chemotherapy surgery. Although long term outcomes remain good, treatments for relapse are associated with increased morbidity. Therefore, we recommend CS1 NSGCT patients with LVI be considered for a single cycle of BEP rather than AS to reduce risk of relapse and prevent relapse related treatment morbidity.(2) References: 1. Daugaard G, Gundgaard MG, Mortensen MS, Agerbaek M, Holm NV, Rorth M, et al. Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort. J Clin Oncol. 2014;32(34):3817-23. 2. Cullen M, Huddart R, Joffe J, Gardiner D, Maynard L, Hutton P, et al. The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis. Eur Urol. 2020;77(3):344-51.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Arasaratnam: Travel/Accommodation/Expenses, educational meeting 2019: Pfizer. H. Gurney: Advisory/Consultancy, Advisory board: BMS; Advisory/Consultancy, Advisory board: Astellas; Advisory/Consultancy, Advisory board: Pfizer; Advisory/Consultancy, Advisory board: MSD; Advisory/Consultancy, Advisory board: Merck; Advisory/Consultancy, Advisory board: Ipsen; Advisory/Consultancy, Advisory board: AstraZeneca. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

213P - Stage I seminoma testicular cancer: Predictors of relapse and outcomes for adjuvant carboplatin vs active surveillance (ID 489)

Presentation Number
213P
Lecture Time
09:00 - 09:00
Speakers
  • Gaik Tin Quah (Newcastle, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Stage 1 (CS1) testicular cancer management has changed dramatically in the last few decades. Seminoma patients now rarely receive adjuvant radiotherapy. Most have adjuvant carboplatin or active surveillance (AS). Tumour size >4cm and rete testis involvement (RTI) have been described as predictive features for relapse but not consistently demonstrated in studies.(1)

Methods

Data on CS1 testicular cancer patients presenting to two sites in Western Sydney between 1990 and 2019 were collected. Tumour characteristics including tumour markers, size of primary, LVI and RTI were correlated with relapse.

Results

Total of 322 cases of CS1 seminoma were identified. 222 received adjuvant radiotherapy and were excluded from this analysis. 2 of 33 (6%) who received carboplatin relapsed compared to 11 of 67 (16%) on AS. All relapsed patients were successfully treated with bleomycin, etoposide and cisplatin (BEP) without recurrence. Two of the AS group died of other causes. RFS at 5 years was 82% and OS 99%. In the AS group, the only parameter statistically associated with relapse was LVI with a hazard ratio (HR) of 3.85 (95% CI 1.01, 14.70, p=0.05). beta HCG elevation (HR 3.89 (95% CI 0.92, 16.50, p=0.07), RTI (HR 0.54 (95% CI 0.11, 2.62, p=0.5) and tumour size of >4cm (HR 0.83 (0.21, 3.22, p=0.8) were not statistically associated with relapse.

Conclusions

Patients with CS1 seminoma have good long term outcomes regardless of first-line management choice. In our series, LVI was associated with relapse of seminoma patients on AS and not tumour size >4cm or RTI. These results further support recent findings on the lack of power and consistency of these tumour characteristics in predicting relapse.(2, 3) Given the lack of any strong prognostic factors for relapse and the good long term outcomes of CS1 seminoma patients regardless of initial treatment, we recommend AS as the management of choice to prevent unnecessary toxicities of adjuvant chemotherapy. References: 1. Warde P et al. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002;20(22):4448-52. 2. Boormans et al. Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of CS1 Seminoma Testis Patients Under Surveillance: a Systematic Review by the Testicular Cancer Guidelines Panel. Eur Urol. 2018;73(3):394-405. 3. Zengerling F et al. Prognostic factors for tumor recurrence in patients with CS1 seminoma undergoing surveillance-A systematic review. Urol Oncol. 2018;36(10):448-58.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Arasaratnam: Travel/Accommodation/Expenses, educational meeting 2019: Pfizer. H. Gurney: Advisory/Consultancy, Advisory board: BMS; Advisory/Consultancy, Advisory board: Astellas; Advisory/Consultancy, Advisory board: Pfizer; Advisory/Consultancy, Advisory board: MSD; Advisory/Consultancy, Advisory board: Merck; Advisory/Consultancy, Advisory board: Ipsen; Advisory/Consultancy, Advisory board: AstraZeneca. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

214P - Study of treatment outcome in adults with TFE related RCC (ID 805)

Presentation Number
214P
Lecture Time
09:00 - 09:00
Speakers
  • Ajaykumar C. Singh (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Translocation renal cell carcinoma (TRCC) represents 1% to 5% of all cases of renal cell carcinoma (RCC), with the highest frequency among children and young adults. Management of these tumors is ill defined. This is a retrospective analysis of treatment outcome in adult patient 18 years or above treated at our hospital between Janaury 2013 to November 2019.

Methods

Clinical and pathological data of 26 patients from a single institution diagnosed with TRCC between January 2013 and November 2019 were retrospectively reviewed. We analyzed our data of patients treated with Surgery only or who progressed after surgery and treated with systemic therapy or who upfront due to unresectable or metastatic disease treated with systemic therapy with respect to Event free survival and overall survival.

Results

Between Jan 2013 to Nov 2018, 26 adult patients were treated at our centre. Out of 26 patients 25 had radical surgery after evaluation and 1 had metastatic disease who was started on systemic therapy. Out 25 patient who were treated with radical surgery, 16 patients progressed and they were started on systemic therapy. Median EFS and median OS among overall population was 22 month and 30 month respectively. Among 16 patient who were treated with systemic therapy, median EFS to first line therapy was 8 month and to second line therapy was 2.5 month. Median OS was 17 month.

Conclusions

TFE RCC is rarely seen but carries significant risk of disease progression with potential response to targeted therapy of short duration.

Legal entity responsible for the study

Ajaykumar Singh.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

215P - Analysis of spatial heterogeneity of responses in metastatic sites with nivolumab in renal cell carcinoma (ID 915)

Presentation Number
215P
Lecture Time
09:00 - 09:00
Speakers
  • Venkata Pradeep Babu Koyyala (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The study was done to appraise whether tumor response to CPI in RCC varies among organs and describe the response patterns in a population of surgically treated metastatic RCC patients treated with Nivolumab.

Methods

A retrospective analysis was conducted in patients receiving Nivolumab for metastatic RCC after first-line therapy, between January 2016 and March 2020, having at least a baseline and two follow up scans. Comparison across groups was performed using a Fisher exact test for categorical variables and a Kruskal-Wallis test for continuous variables. TTP was estimated using a Kaplan-Meier method.

Results

21 out of 30 patients analyzed were eligible and were classified into two arms as either responder ( n=11) or non-responders ( n=10). Of the 21 patients, 18 (85.7 %) had the following: PD (10 patient), PR (3 patients) and SD (8 patients) according to all iRECIST guidelines. Overall, 7, 15, 4, 13, 7, and 7 patients had measurable hepatic metastasis and lung, brain, lymph node, soft tissue and other intra-abdominal metastases at baseline, respectively; these patients were subject to organ-specific response evaluation. Organ-specific ORRs of hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals and other intra-peritoneal metastases were 10, 19, 20, 35, 0, 25 and 25%, respectively. Among them, 13 (61.9%) exhibited differential responses to CPI treatment with 6 (28.5 %) patients revealing intra – organ differential response. The best objective response (BOR) was seen in lymph nodes (35%), followed by adrenals and peritoneal (25 % both) followed by the brain (20%) and lung (19%). The response rate was highest in adrenal gland lesions (2/4; 50%) followed by lymph nodes (13/19; 68.4 %) and liver ( 5/10; 50 %), while the rates were intermediate in lung (9/25; 36 %), intraperitoneal metastasis ( 1/4; 25%), brain (1/5; 20 %), and lowest in soft tissue (1/7; 14.2 %) lesions.

Conclusions

There is a differential response to checkpoint inhibitors at different metastatic sites in Renal Cell carcinoma, With highest Best response in Lymph nodes and least in soft tissue.

Legal entity responsible for the study

Rajiv Gandhi Cancer Institute and Research Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

216P - Clinical profile and treatment outcome of testicular seminoma treated at tertiary care centre in Chennai (ID 558)

Presentation Number
216P
Lecture Time
09:00 - 09:00
Speakers
  • Sivasubramaniam Kumaravelu (Chennai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Seminomas form around 50% of germ cell tumours of testes. It commonly occurs during third decade. It is highly chemo sensitive and radio sensitive. Those patients who recur during surveillance for early stage can be salvaged by treatment with chemotherapy or radiotherapy most of the times.

Methods

Data was collected from master case sheets of seminoma patients treated over a period of five years from January 2013 to December 2017 at department of Madras medical college, Chennai.

Results

28 patients had seminoma of testes with a median age of 37 years. All patients had classical type histopathology. Right testis was more commonly involved (n=21) than left (n=7). 4 patients had seminoma arising from undescended testes. 10.7% (n=3) patients had elevated beta hcg and 28.5% (n=8) had elevated LDH. 9 patients had stage I, 12 patients had stage II and 7 patients had stage III disease. 3 patients had trans scrotal violation at peripheral hospital. 6 patients with stage I received paraaortic nodal irradiation with a mean dose of 24Gy of which 3 patients received inguinal irradiation also. All stage II and stage III patients received adjuvant chemotherapy with BEP regimen with minimum of 3 cycles. 2.5 year DFS and OS in stage I was 88.9% (n=8) and 100% (n=9) respectively. 2.5 year DFS and OS in stage II was 83.3% (n=10) and 91.6% (n=11) respectively. 2.5 year DFS and OS was 71.4% (n=5) and 71.4% (n=5) respectively.

Conclusions

Patients presented with advanced stage compared to that given in literature due to ignorance. Treatment results were comparable with that given in the literature.

Legal entity responsible for the study

Sivasubramaniam Kumaravelu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO13 - An extremely high alpha-fetoprotein producing Adrenal Hepatoid Adenocarcinoma: A case report (ID 189)

Presentation Number
YO13
Lecture Time
09:00 - 09:00
Speakers
  • Tawasapon Thambamroong (Bangkok, Thailand)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

Hepatoid adenocarcinoma (HAC) is a rare tumor with produces an alpha-fetoprotein (AFP) mimics Hepatocellular Carcinoma (HCC). Adrenal HAC is exceeding rare. Here we report the extremely high alpha-fetoprotein (AFP) producing adrenal HAC, the first case report of Thailand.
A 47-year-old male presented with severe left flank pain and progressive dyspnea for 2 months. He also lost his bodyweight for 15 kg within 2 months. Physical examination showed a huge mass at the left flank area by bimanual palpation. CT scan of the whole abdomen revealed a 5.5 x 7 cm enhancing mass involving the left adrenal gland and left hemidiaphragm, a 3.7 x 3.3 cm early enhancing mass at liver segment VII on arterial phase and rapid washout on porto-venous phase, and multiple hypodense masses in both lobes of the liver. AFP level was 321,495 ng/mL. A liver biopsy was done. This patient was diagnosed with advanced adrenal hepatoid adenocarcinoma due to the immunohistochemistry studies (IHC) positive for AE1/AE3, CAM5.2, Arginase-1, and Glypican-3 but negative for CK7, CK20, CK19, Inhibin A, Chromogranin A, Synaptophysin, S100, and HepPar-1. Unfortunately, the tumor was progression and involving through the stomach. He developed massive upper-GI bleeding and passed away 3 weeks after diagnosis.
Adrenal HAC is an extremely rare cancer. It is difficult to diagnosis which HCC, paraganglioma, and pheochromocytoma should be excluded. Surgical resection is preferred if resectable condition. However, there is no standard treatment for systemic therapy.

Editorial acknowledgement

Acknowledge to Phramongkutklao Hospital (PMK) Tumour Board, Medical Oncology division, Endocrinology division, and Clinical Nutrition division, Department of Internal medicine, Department of Pathology, and Department of Radiology for collaborating to diagnose and treat this patient

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e-Poster Display Session (ID 87) Poster Display

Genitourinary tumours, prostate (ID 1148)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

220P - A cost-effectiveness analysis of systemic therapy for metastatic hormone-sensitive prostate cancer (ID 262)

Presentation Number
220P
Lecture Time
09:00 - 09:00
Speakers
  • Winnie W. Sung (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The treatment paradigm of metastatic hormone-sensitive prostate cancer (mHSPC) has significantly changed over the past decade. Currently, approved first-line treatment options include (1) androgen deprivation therapy (ADT) alone, ADT plus one of the following: (2) docetaxel, (3) abiraterone, (4) enzalutamide, and (5) apalutamide. The high cost of novel androgen receptor pathway inhibitors warrants an understanding of the combinations’ value by considering both efficacy and cost. The objective of this study was to compare the cost-effectiveness of these treatment options in mHSPC from the US payer perspective to guide treatment sequence.

Methods

A Markov model was developed to compare the lifetime cost and effectiveness of ADT alone, docetaxel plus ADT, abiraterone plus ADT, enzalutamide plus ADT, and apalutamide plus ADT in the first-line treatment of mHSPC using outcomes data from published literature. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were obtained from the Veterans Affairs Pharmaceutical Catalog in 2020 US dollars. We extrapolated survival beyond closure of the trials. Model robustness was addressed in univariable and probabilistic analyses. A willingness-to-pay (WTP) threshold of US$100,000 per QALY was used.

Results

Compared to ADT alone, docetaxel plus ADT provided a 0.31 QALY gain at an ICER of US$1,542 per QALY. Abiraterone plus ADT provided an additional 1.29 QALYs against docetaxel plus ADT, with an ICER of US$26,416 per QALY. Compared to abiraterone plus ADT, enzalutamide plus ADT provided an additional 0.06 QALYs at an ICER of US$3,826,216 per QALY. Given the WTP threshold of US$100,000 per QALY, abiraterone plus ADT represented high-value health care

Base case results

Strategy Total Incremental ICER (US$/QALY)
Cost (US$) QALYs Life-years Cost (US$) QALYs
ADT only 97,767 3.56 4.70 --- --- Baseline
DCX + ADT 98,237 3.87 5.08 470 0.31 1,542
AA + ADT 132,403 5.16 6.45 34,165 1.29 26,416
APA + ADT 300,891 4.14 5.30 --- --- Dominated
ENZ + ADT 366,476 5.22 6.51 234,073 0.06 3,826,216

QALY=quality-adjusted life-year; ICER=incremental cost-effectiveness ratio; DCX=docetaxel; ADT=androgen deprivation therapy; AA=abiraterone; APA=apalutamide; ENZ=enzalutamide.

.

Conclusions

Abiraterone plus ADT is the preferred treatment option for men with mHSPC at a WTP threshold of US$100,000 per QALY.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

221P - Patient-reported sexual and urinary function in nonmetastatic castration-resistant prostate cancer (nmCRPC) when treated with apalutamide (APA) vs placebo (PBO) and ongoing androgen deprivation therapy (ADT) in SPARTAN (ID 629)

Presentation Number
221P
Lecture Time
09:00 - 09:00
Speakers
  • Hiroji Uemura (Yokohama, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

SPARTAN is a phase III trial that evaluated the efficacy of APA vs PBO in pts with nmCRPC with a prostate-specific antigen doubling time of ≤ 10 mo. At primary analysis, APA significantly improved metastasis-free survival and extended time to metastasis, progression-free survival, and time to symptomatic progression vs PBO (Smith MR, et al. N Engl J Med. 2018) while preserving health-related quality of life (Saad F, et al. Lancet Oncol. 2018). At final analysis, APA significantly improved overall survival and time to chemotherapy vs PBO (Small ASCO 2020). We evaluated sexual and urinary function in SPARTAN.

Methods

A total of 1207 pts were randomized 2:1 to APA (240 mg once daily) or PBO. Sexual and urinary function HRQoL was assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P) response items collected at baseline and Day 1 of: cycle 1 (pre-dose), cycles 2-6, every 2 cycles from 7 to 13, every 4 treatment cycles thereafter, end of treatment, and every 4 months post progression for up to 1 year. Each cycle was 28 d. Descriptive statistics are reported. At each cycle, the number of patients with stable and improved FACT-P scores were summed; mean percentage (range) for APA and PBO were calculated separately.

Results

Median follow-up was 52 mo; median treatment durations were 32.9 mo (APA) and 11.5 mo (PBO). At each cycle, > 90% of all eligible pts completed the questionnaire. Patients receiving APA generally reported stable or improved sexual and urinary function over time during treatment (table). Compared with PBO, a slightly larger proportion of APA-treated patients maintained erectile and urinary functioning compared with baseline or showed improvement over time.

Conclusions

Health-related quality of life data from SPARTAN indicate that baseline sexual and urinary function in pts with nmCRPC is preserved during APA + ADT therapy.

Fact-P item Favorable responses at baseline,a % Mean % stable or improved (range across cycles)
APA + ADT PBO + ADT APA + ADT PBO + ADT
GS7: I am satisfied with my sex life 19 23 43 (41-46) 46 (44-48)
BL5: I am able to have and keep an erection 15 14 86 (84-88) 82 (76-88)
P7: I have difficulty urinating 61 61 83 (79-87) 77 (70-84)
BL2: I urinate more frequently than usual 27 26 74 (70-78) 71 (65-77)
P8: My problems with urinating limit my activities 60 60 78 (73-81) 75 (68-85)

aBaseline data for GS7 and BL5 includes “a little bit,” “somewhat,” “quite a bit,” or “very much”; baseline data for P7, BL2, and P8 includes “not at all.”

.

Clinical trial identification

SPARTAN: NCT01946204.

Editorial acknowledgement

William Turner, PhD Parexel International.

Legal entity responsible for the study

Janssen Research and Development.

Funding

Janssen Research and Development.

Disclosure

H. Uemura: Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): FRI-Toyama chem; Honoraria (self), Advisory/Consultancy, Leadership role, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Research grant/Funding (institution): Kyowa-Kirin; Honoraria (self), Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda. S. Oudard: Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Research grant/Funding (self): Ipsen; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Sanofi. B.A. Hadaschik: Honoraria (self), Advisory/Consultancy: ABX; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): German Cancer Aid; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Lightpoint Medical; Honoraria (self), Advisory/Consultancy: Pfizer. F. Saad: Honoraria (self): AbbVie; Honoraria (self): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca / MedImmune; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi. D. Cella: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Honoraria (self), Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Clovis; Officer/Board of Directors: FACIT.org; Honoraria (self), Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer. E. Basch: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: CareVive Systems; Advisory/Consultancy: Dana-Farber Cancer Institute; Officer/Board of Directors: Journal of the American Medical Association; Advisory/Consultancy: Memorial Sloan Kettering Cancer Center; Advisory/Consultancy: Research Triangle Institute; Advisory/Consultancy: Sivan Healthcare. J.N. Graff: Honoraria (self), Research grant/Funding (institution): Astellas; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Travel/Accommodation/Expenses: Clovis Oncology; Advisory/Consultancy: Exelixis; Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Medivation; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme; Licensing/Royalties: Oncoresponse: Exceptional Responders; Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi. S. Dibaj: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. S. Li: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. S.D. Brookman-May: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: JohnsonJohnson. P. De Porre: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: JohnsonJohnson. K. Bevans: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: JohnsonJohnson. J. Trudeau: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. M.R. Smith: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (self): Gilead; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. E.J. Small: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Fortis; Shareholder/Stockholder/Stock options: Harpoon Therapeutics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (self): Merck Sharp & Dohme. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

222P - Tolerability and treatment response to darolutamide (DARO) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the phase III ARAMIS trial (ID 711)

Presentation Number
222P
Lecture Time
09:00 - 09:00
Speakers
  • Matthew R. Smith (Boston, MA, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Androgen receptor inhibitors (ARIs) approved for treating nmCRPC are associated in varying degrees with certain adverse events (AEs), e.g., fatigue, risk of falls or rash. In phase III studies, dose modification and discontinuation due to AEs was higher with ARIs vs placebo. Reduced dose, compliance patterns and treatment adherence may impact drug efficacy. Tolerability of DARO and association of prostate-specific antigen (PSA) decline in response to DARO treatment with metastasis-free survival (MFS) in the ARAMIS trial are reviewed.

Methods

1509 patients with nmCRPC and PSA doubling time (PSADT) ≤10 months were randomised 2:1 to DARO 600 mg twice daily (n=955) or placebo (PBO; n=554) while continuing androgen deprivation therapy. AEs and dose modifications were assessed every 16 weeks. The association between PSA decline from baseline in response to DARO treatment and MFS was evaluated using the Cox proportional hazards model. An association with overall survival will be investigated.

Results

DARO was well tolerated; 97.2% of patients on DARO received the full planned dose. Permanent treatment discontinuation due to AEs was similar for patients treated with DARO as compared with PBO (8.9% vs 8.7%). Few patients had dose modifications for AEs or any other reason (15.2% vs 9.7% for DARO vs PBO). Almost all of the patients on DARO who had dose interruptions or modifications were able to resume and re-establish the indicated dose (91.7% vs 88.9% for DARO vs PBO). In the ARAMIS trial, 50.9% of patients on DARO had a maximal PSA response (≥90% decrease from baseline) vs 1.8% of patients on PBO. Pharmacodynamic modelling showed that longer MFS was positively associated with maximum decrease in PSA from baseline. Prostate cancer-related quality of life was maintained with DARO treatment.

Conclusions

Favourable tolerability of DARO at the recommended dose of 600 mg twice daily was associated with low rates of dose reduction and treatment discontinuation, which in turn may lead to extended survival with longer duration of treatment with DARO. It is important to further assess the real-world tolerance of different ARIs in men with nmCRPC.

Clinical trial identification

NCT02200614.

Editorial acknowledgement

Editorial assistance was provided by Lucy Smithers, PhD, and Annabel Ola, MSc, both of Scion, London, and supported by Bayer.

Legal entity responsible for the study

Bayer AG and Orion Pharma.

Funding

Bayer AG and Orion Pharma.

Disclosure

M.R. Smith: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Amgen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Lilly; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer. N.D. Shore: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy: Tolmar; Advisory/Consultancy: Ferring; Advisory/Consultancy: Medivation; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Myovant Sciences; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Dendreon. T.L.J. Tammela: Research grant/Funding (institution): Bayer; Advisory/Consultancy: Janssen; Research grant/Funding (institution): Lidds AB; Research grant/Funding (institution): Astellas Pharma. M-A. Le Berre: Full/Part-time employment: Bayer. O. Petrenciuc: Full/Part-time employment: Bayer. C. Zurth: Full/Part-time employment: Bayer. I. Kuss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer. K. Fizazi: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Orion Pharma GmbH; Advisory/Consultancy: Curevac; Honoraria (institution): AstraZeneca; Advisory/Consultancy: ESSA; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: Roche.

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e-Poster Display Session (ID 87) Poster Display

223P - Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for non-metastatic castration-resistant prostate cancer (nmCRPC) (ID 740)

Presentation Number
223P
Lecture Time
09:00 - 09:00
Speakers
  • Karim Fizazi (Villejuif, France)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

DARO is a structurally distinct androgen receptor inhibitor with a favourable safety profile, approved for treating men with nmCRPC after demonstrating significantly prolonged metastasis-free survival, compared with placebo (PBO), in the phase III ARAMIS trial: median 40.4 vs 18.4 months, respectively (HR 0.41; 95% CI 0.34–0.50; P<0.0001). We report final analyses of OS, all other secondary endpoints, and updated safety results.

Methods

1509 patients (pts) with nmCRPC were randomized 2:1 to DARO 600 mg twice daily (n=955) or PBO (n=554) while continuing ADT. Secondary endpoints included OS, times to pain progression, first cytotoxic chemotherapy, and first symptomatic skeletal event. OS analysis was planned to occur after approximately 240 deaths. Secondary endpoints were evaluated in a hierarchical order.

Results

Final analysis was conducted after 254 deaths (15.5% of DARO and 19.1% of PBO pts). After unblinding at primary analysis, 170 pts crossed over from PBO to DARO. The majority of pts originally randomised to PBO (56%, including crossover pts) received a subsequent life-prolonging therapy vs 15% of pts randomised to DARO. Of pts who discontinued study treatment, the majority received subsequent docetaxel (16.8% (82/488) of DARO and 13.5% (75/554) of PBO pts).

DARO showed a statistically significant OS benefit corresponding to a 31% reduction in the risk of death vs PBO (HR 0.69; 95% CI 0.53–0.88; P=0.003), regardless of effect of crossover and subsequent therapies. All other secondary endpoints were significantly prolonged by DARO. Incidences of treatment-emergent adverse events (AEs) with ≥5% frequency were similar to those observed at primary analysis. Incidences of AEs of interest (including falls, mental impairment, and hypertension) were not increased with DARO compared with PBO when adjusted for treatment exposure.

Conclusions

DARO significantly improved OS vs PBO in men with nmCRPC. In addition, DARO delayed onset of cancer-related symptoms and subsequent chemotherapy vs PBO. With longer follow-up, safety and tolerability were favourable and consistent with the primary ARAMIS analysis.

Clinical trial identification

NCT02200614.

Editorial acknowledgement

Editorial assistance was provided by Lucy Smithers, PhD, and Annabel Ola, MSc, both of Scion, London, and supported by Bayer.

Legal entity responsible for the study

Bayer AG and Orion Pharma.

Funding

Bayer AG and Orion Pharma.

Disclosure

K. Fizazi: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Orion Pharma GmbH; Advisory/Consultancy: Curevac; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: ESSA; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: Roche. N.D. Shore: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy: Tolmar; Advisory/Consultancy: Ferring; Advisory/Consultancy: Medivation; Advisory/Consultancy: Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Myovant Sciences; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Dendreon. T.L.J. Tammela: Research grant/Funding (institution): Bayer; Advisory/Consultancy: Janssen; Research grant/Funding (institution): Lidds AB; Research grant/Funding (institution): Astellas Pharma. E. Vjaters: Advisory/Consultancy, Research grant/Funding (institution): Orion; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Ipsen. M. Jievaltas: Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Ipsen. M. Luz: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Myovant Sciences. B. Alekseev: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ferring; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): ICON Clinical Research. I. Kuss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bayer. M-A. Le Berre: Full/Part-time employment: Bayer. O. Petrenciuc: Full/Part-time employment: Bayer. A. Snapir: Full/Part-time employment: Orion Corporation. T. Sarapohja: Full/Part-time employment: Orion. M.R. Smith: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

224P - Associations of pre-existing cardiovascular disease (CVD) with treatment patterns and survival outcomes in patients with localized prostate cancer: A real-world, population-based study (ID 250)

Presentation Number
224P
Lecture Time
09:00 - 09:00
Speakers
  • Atul Batra (New Delhi, Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Research has largely focused on the effect of prior androgen deprivation therapy on the subsequent risk of CVD in patients with metastatic prostate cancer. However, the impact of pre-existing CVD on localized prostate cancer treatments and outcomes is unknown. This study aimed to identify the associations of baseline CVD with treatment patterns and survival outcomes in localized prostate cancer.

Methods

We identified patients diagnosed with localized prostate cancer in a large Canadian province from 2004-2017 using the population-based registry. Administrative sources were linked to ascertain any diagnoses of CVD (including myocardial infarctions [MIs], congestive heart failure [CHF], cerebrovascular accidents [CVAs] and arrythmias [AR]) prior to the onset of prostate cancer. Logistic regression and Cox regression were used to determine the associations of baseline CVD with cancer treatments (receipt of surgery and radiotherapy) and overall survival (OS).

Results

A total of 23,670 patients were included. The median age was 65 years (interquartile range, 38-97 years). Of these, 16.4%, 71.1% and 12.5% patients had stage I, II and III prostate cancer, respectively. At the diagnosis of prostate cancer, 4860 (20.5%) had pre-existing CVD: 6.0% AR, 3.4% CVAs, 3.0% MIs, 1.8% CHF and 6.4% multiple CVDs. The Charlson comorbidity index (CCI) was 0, 1 and >1 in 55.3%, 25.4% and 19.3%. After adjusting for age, stage and CCI, pre-existing CVD was associated with a lower likelihood of surgery (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.81-0.95; P=0.001), but not radiotherapy (OR, 0.96; 95% CI, 0.88-1.04; P=0.319). Likewise, CVD was associated with worse OS, after adjusting for measured confounding variables (Table).

Hazard ratio 95% confidence interval P-value
Age at diagnosis < 65 > 65 Ref 3.55 3.29-3.83 <0.001
Stage at diagnosis I II III Ref 1.33 1.52 1.18-1.51 1.30-1.77 <0.001 <0.001
Surgery No Yes Ref 0.59 0.55-0.63 <0.001
Radiotherapy No Yes Ref 0.52 0.48-0.56 <0.001
Baseline cardiovascular disease No Yes Ref 1.97 1.85-2.10 <0.001

Conclusions

One-fifth of patients with localized prostate cancer have pre-existing CVD, which was associated with a lower likelihood of surgery and worse OS. In the context of an aging general population, this may have implications for radiotherapy capacity planning as more patients are offered non-surgical therapies. Early cardio-oncology consultations may optimize the management of CVD and allow for better uptake of prostate cancer treatments.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

225P - Prostate cancer treatments and outcomes in the elderly: A retrospective analysis of an Australian real-world cohort (ID 682)

Presentation Number
225P
Lecture Time
09:00 - 09:00
Speakers
  • Michael Fernando (Box Hill, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Elderly men (>/=75yo) comprise 25% of patients with prostate cancer. However, they are typically underrepresented in pivotal trials. Limited data suggest these patients receive less intensive treatment with greater toxicity, despite comparable response rates. Our retrospective study examined treatment patterns and outcomes in a real-world population with castration-resistant prostate cancer (CRPC).

Methods

Using the multi-centre electronic CRPC Australian Database (ePAD), we extracted clinicopathologic, treatment and outcome data. Descriptive statistics were used to report data in patients aged >/=75yo and <75yo. Comparisons between these groups were analysed using T-tests and Fisher’s exact tests. Time-to-event analyses were performed using the Kaplan-Meier method.

Results

We identified 753 men with CRPC, with 327 (43%) aged >/=75yo. Elderly patients had higher rates of ischemic heart disease (33% vs 16% in younger patients, p=0.004) and stroke (11% vs 5%, p=0.007). They were more likely to receive only one line of systemic therapy (67% vs 40%, p<0.001), and androgen receptor signalling inhibitors (ARSIs) were most commonly prescribed as initial therapy (78% vs 48%, p<0.001). Enrolment in clinical trials was less frequent (5% vs 15%, p<0.001). There was no statistical difference in treatment duration or PSA50 response rates with ARSIs or docetaxel (Table). Overall, serious adverse events (SAEs) leading to hospitalisation, dose delays or modifications occurred in more elderly men (24% vs 16%, p=0.003), with a trend towards greater SAEs in those receiving docetaxel or ARSIs. Elderly patients were more likely to stop docetaxel due to toxicity (39% vs 21%, p=0.02).

First-line therapy for CRPC

<75yrs >/=75years p-value
Abiraterone N=58 N=84
PSA50 response rate 24 (41%) 43 (51%) 0.30
Treatment duration 11.9 months 10.6 months 0.52
Serious adverse event 10 (17%) 24 (29%) 0.16
Cessation due to toxicity 6 (10%) 12 (14%) 0.61
Enzalutamide N=119 N=159
PSA50 response rate 63 (53%) 94 (59%) 0.33
Treatment duration 11.5 months 11.5 months 0.87
Serious adverse event 20 (17%) 36 (23%) 0.29
Cessation due to toxicity 8 (7%) 16 (10%) 0.39
Docetaxel N=155 N=41
PSA50 response rate 79 (51%) 18 (44%) 0.48
Treatment duration 6.0 months 4.6 months 0.24
Serious adverse event 28 (18%) 10 (24%) 0.38
Cessation due to toxicity 32 (21%) 16 (39%) 0.02
.

Conclusions

In our real-world cohort, elderly men had greater comorbidities and received fewer lines of systemic therapy. Although there was no difference in treatment response or duration, elderly patients experienced higher SAE rates. Prospective studies are required to further evaluate long-term outcomes in these patients.

Legal entity responsible for the study

The authors.

Funding

Astellas, AstraZeneca, Janssen, Amgen.

Disclosure

E. Kwan: Honoraria (self): Janssen; Honoraria (self), Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Merck Serono. F.X. Parnis: Leadership role, Administrative Board: Janssen; Leadership role, Administrative Board: Astellas; Leadership role, Administrative Board: Bayer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

226P - Use of PSMA PET in metastatic castration-resistant prostate cancer (mCRPC) (ID 698)

Presentation Number
226P
Lecture Time
09:00 - 09:00
Speakers
  • Andrew Jensen (Melbourne, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Prostate-specific membrane antigen (PSMA) PET/CT has demonstrated greater sensitivity than conventional imaging including CT Chest, Abdomen and Pelvis (CT CAP) and whole body bone scan (WBBS) in the detection of metastatic prostate cancer. While there is limited data supporting a role in the staging of mCRPC, PSMA PET/CT is increasingly performed in this setting. Given the recent approval of novel therapeutic agents for non-metastatic (M0) CRPC, based on CT and WBBS findings, the increased accuracy of PSMA PET/CT is likely to alter the M0 population and influence the use of these treatments. Our study examines the impact of PSMA PET/CT in Australian mCRPC patients.

Methods

The multi-centre electronic CRPC Australian database (ePAD) was interrogated to identify mCRPC patients with available PSMA PET/CT for central review, prior to first line treatment for CRPC. Findings from PSMA PET, concurrent CT (with or without contrast) and whole body bone scan (WBBS) were analysed, particularly metastatic sites including pelvic lymph nodes (LN), distant LN, bone and viscera. Descriptive statistics were used to report differences between PSMA PET/CT, conventional CT and/or WBBS.

Results

Of the 603 eligible patients enrolled within ePAD between 2016 and 2019, 90 (15%) had mCRPC and an available PSMA PET/CT for central review. Fifteen (17%) also had dedicated CT imaging, 8 (9%) had concurrent WBBS, 10 (11%) had both dedicated CT and WBBS, while 57 (63%) only had concurrent low dose CT. Within our mCRPC PSMA PET cohort 10 (11%) had M0 disease based on CT and/or WBBS, in whom metastatic disease was only detected by PSMA PET/CT. Nine of these patients subsequently commenced systemic therapy. PSMA PET identified additional metastases in 39 (43%) patients when compared to CT and/or WBBS, including 29 (29%) patients in whom additional metastatic sites were identified PSMA PET most commonly detected additional bone metastases (28%) followed by pelvic LN (15%) or distant LN (8%).

Conclusions

In our real-world cohort, PSMA PET/CT was commonly performed without conventional imaging for mCRPC. PSMA PET/CT also demonstrated increased sensitivity for detection of metastases. The clinical impact of treatment decisions based on PSMA PET/CT findings in mCRPC requires further evaluation.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

227P - Phase II study of pembrolizumab (pembro) plus enzalutamide for enzalutamide (enza)-resistant metastatic castration-resistant prostate cancer (mCRPC): Cohorts (C) 4 and 5 update from KEYNOTE-199 (ID 788)

Presentation Number
227P
Lecture Time
09:00 - 09:00
Speakers
  • Ulka N. Vaishampayan (Ann Arbor, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy-naive patients (pts) with mCRPC who had disease progression with enza were enrolled in C4 and C5 of the multicohort phase II KEYNOTE-199 study (NCT02787005).

Methods

Pts who did or did not previously take abiraterone acetate were eligible if they developed resistance to enza after prior response. Cohorts were composed of pts who had RECIST-measurable (C4) or bone-predominant nonmeasurable (C5) disease. Pts received pembro 200 mg Q3W for up to 35 cycles + enza QD until progression, toxicity, or withdrawal. The primary end point was ORR per RECIST v1.1 by blinded independent central review in C4; DOR was also analyzed. Secondary end points (both cohorts) were DCR, rPFS, OS, time to cytotoxic chemotherapy, time to new anticancer therapy, and safety.

Results

A total of 126 pts (C4, 81; C5, 45) were treated. Median (range) time from enrollment to data cutoff was 15 mo (7-21) and 19 mo (7-21) in C4 and C5, respectively. In C4, ORR (95% CI) was 12% (6-22) (2 CRs, 8 PRs) and median (range) DOR was 6.3 mo (2.5+ to 13.4); 4 responders (73% by Kaplan-Meier estimation) had a response ≥6 mo (Table). Median time to cytotoxic chemotherapy was 11.1 and 11.3 mo in C4 and C5, and time to PSA progression was 4.2 mo in both cohorts (Table). A total of 26% and 24% of pts in C4 and C5, respectively, experienced grade ≥3 treatment-related adverse events (TRAEs). Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any-grade/grade 3 or 4 rash (33%/6%), regardless of treatment relatedness, was higher than previously reported for individual agents but manageable with standard-of-care treatments.

Efficacy outcomes

Cohort 4 RECIST Measurable N = 81 Cohort 5 Bone Predominant Nonmeasurable N = 45
ORR, by RECIST v1.1 by BICR, n/N (%) 10/81 (12) NA
DCR, n/N (%) 41/81 (51) 23/45 (51)
PSA response rate in patients with baseline PSA, n/N (%) 13/80 (16) 4/45 (9)
Time to PSA progression
Median (95% CI),a mo 4.2 (4.1-4.4) 4.2 (4.2-4.4)
rPFS
Median (95% CI),a mo 4.2 (2.5-6.0) 4.4 (3.4-6.2)
rPFS 12 mo, % 17 23
OS
Median (95% CI),a mo NR (15.9-NR) 18.8 (14.0-NR)
OS 12 mo, % 70 75
Time to cytotoxic chemotherapy
Median (95% CI),a mo 11.1 (8.5-NR) 11.3 (9.0-14.5)
Event-free survival 12 mo, % 47 47
Time to new anticancer therapy
Median (95% CI),a mo 9.4 (7.2-11.1) 9.5 (5.9-12.1)
Event-free survival 12 mo, % 38 35

Conclusions

After enza resistance, pembro + enza showed antitumor activity and manageable safety for RECIST-measurable and bone-predominant mCRPC. Pembro + enza is being evaluated in the ongoing phase III KEYNOTE-641 trial (NCT03834493)..

Clinical trial identification

NCT02787005, June 1, 2016.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

U.N. Vaishampayan: Advisory/Consultancy, Research grant/Funding (self): Merck & Co., Inc. T. Elliott: Research grant/Funding (self), Research grant/Funding (institution): Per-patient payments, Pfizer, Bayer, Astellas, AstraZeneca, Janssen, Travel/Accommodation/Expenses: Janssen. A.G. Omlin: Advisory/Consultancy: Astellas, Bayer, Sanofi, Roche, Janssen, MSD, Molecular Partners; Speaker Bureau/Expert testimony: Astellas, Janssen, Bayer; Travel/Accommodation/Expenses: Astellas, Bayer, Sanofi, Janssen; Research grant/Funding (institution): Teva, Janssen. J.N. Graff: Advisory/Consultancy: Sanofi, Astellas, Bayer, Valeant, Janssen; Travel/Accommodation/Expenses: Sanofi, Clovis, Janssen, Bayer. C.J. Hoimes: Honoraria (self): BMS, Genentech, Seattle Genetics; Advisory/Consultancy: Seattle Genetics, Merck, 2bPrecise; Speaker Bureau/Expert testimony: BMS, Genentech, Seattle Genetics, Eisai; Research grant/Funding (institution): Merck, Seattle Genetics, Genentech, Novartis, Astellas; Travel/Accommodation/Expenses: Sanofi, Clovis, Janssen, Bayer. S.T. Tagawa: Honoraria (self): Sanofi, Medivation/Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, AbbVie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Genomic Health, Point Pharma, Ambrx; Research grant/Funding (institution): Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, AbbVie, Karyopharm, Endocyte, Clovis, Seattle Geneti; Travel/Accommodation/Expenses: Amgen, Sanofi, Immunomedics. R.S. McDermott: Advisory/Consultancy: Bristol-Myers Squibb, Merck, Genentech/Roche, Pfizer Exelixix, Novartis, Array BioPharma, Peloton Therapeutics, EMD Serono, Jounce Therapeutics, Alkermes, Lilly, Eisai; Research grant/Funding (institution): Prometheus Laboratories, Bristol-Myers Squibb, Merck, Genentech, Novartis, Alkermes, Peloton Therapeutics; Honoraria (self), Other: BIDMC; Non-remunerated activity/ies: X4 Pharmaceuticals, AVEO. W.R. Gerritsen: Advisory/Consultancy: BMS, Iqvia, Bayer, MSD, Sanofi, Janssen-Cilag; Speaker Bureau/Expert testimony: MSD; Research grant/Funding (self): Astellas, Bayer, Janssen-Cilag, Sanofi. H. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck. J. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J.S. de Bono: Advisory/Consultancy: AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Genentech/Roche, Janssen Oncology, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, Bayer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, GlaxoSmi; Research grant/Funding (institution): AstraZeneca, Genentech, Sanofi, Taiho Pharmaceutcials, Daiichi Sankyo, Merck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma, GlaxoSmithKline, Cellcentric, Celgene, Sierra Oncology, Bayer, MedImmune, Medivation, Terumo, Astellas Pharma, G. E.S. Antonarakis: Research grant/Funding (self): Janssen, Sanofi, Dendreon, AstraZeneca, Clovis, Merck, JohnsonJohnson, Genentech, Novartis, Bristol-Myers Squibb, Tokai, Celgene; Advisory/Consultancy: Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, Merck, Lilly, Amgen, Bayer, GlaxoSmithKline; Licensing/Royalties: Qiagen. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

228P - Symptoms and impacts of metastatic castration-resistant prostate cancer (mCRPC) among Japanese patients designated to receive Ra-223 (ID 520)

Presentation Number
228P
Lecture Time
09:00 - 09:00
Speakers
  • Hiroji Uemura (Yokohama, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Radium-223 (Ra-223) received regulatory approval for castration-resistant prostate cancer (CRPC) with bone metastasis in Japan in 2016. This study aimed to reveal emerging symptoms, impacts, and concerns within the Japanese patient experience of living with mCRPC and the burden of bone metastasis prior to Ra-223 treatment, through patient and physician interviews.

Methods

This non-interventional, qualitative study consisted of interviews with 23 bone metastatic CRPC patients prior to their first Ra-223 treatment cycle, and 3 treating physicians in Japan. Patients were recruited via purposive sampling. Inclusion criteria were: (1) a diagnosis of bone metastatic CRPC, and (2) designated to start receiving Ra-223 in routine clinical practice. Physicians included those who had prescribed at least one Ra-223 treatment cycle in the past 12 months and are currently prescribing Ra-223. All interview data were entered into ATLAS.ti v8.0 for coding, assessment of concept frequency, themes and saturation analysis.

Results

The patients’ mean age was 75.8 y.o., with 45% symptomatic at the time of enrolment. Forty-seven mCRPC symptoms were reported, including pain, fatigue, nocturia, muscle loss, and various side effects related to previous PC treatment and/or disease stage. Around mCRPC diagnosis, patients reported back pain (45%), hip pain (23%) and pain specifically in their bones (27%). Life impacts reported included 45 concepts, with the most frequently mentioned being worry for their disease progression and how it would impact their family and lives, the impact that mCRPC has on their daily, physical abilities (e.g. difficulty walking, muscle loss) and the impact a patients’ mCRPC has on the family and caregivers. Patients had high expectations from Ra-223 in terms of cessation of disease progression (32%) and pain alleviation (23%), but also worry about adjusting to the treatment. All 3 physicians cited the need for information sharing about Ra-223.

Conclusions

The symptoms and impacts of living with mCRPC and the associated burden of bone metastasis and skeletal-related symptoms are considerable and varied, and information sharing is key to easing concerns in utilizing Ra-223 treatment.

Legal entity responsible for the study

Bayer Yakuhin, Ltd.

Funding

Bayer Yakuhin, Ltd.

Disclosure

H. Uemura: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen Pharmaceutical; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer Yakuhin, Ltd.; Honoraria (self), Speaker Bureau/Expert testimony: Astellas Pharmaceutical; Honoraria (self), Speaker Bureau/Expert testimony: Takeda Pharmaceutical; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca Pharmaceutical. K. Akakura: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer Yakuhin, Ltd.; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas Pharmaceutical; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Takeda Pharmaceutical; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca Pharmaceutical; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen Pharmaceutical. A. Stroupe, C. Seo, A. Uzumcu, K. McCarrier: Advisory/Consultancy: Bayer Yakuhin, Ltd. D. Ledesma: Full/Part-time employment: Bayer Yakuhin, Ltd. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

229P - Expanding the role of supervised exercise on fatigue in prostate cancer patient receiving androgen deprivation therapy: A meta-analysis of randomized controlled trial (ID 553)

Presentation Number
229P
Lecture Time
09:00 - 09:00
Speakers
  • Niwanda Yogiswara (Surabaya, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Fatigue is a common adverse effect suffered by prostate cancer patients receiving androgen deprivation therapy (ADT). A growing body of evidence has proposed exercise as a treatment to relieve and prevent the adverse effects of ADT. Recently, high-quality randomized controlled trials (RCTs) of supervised exercise have been conducted to get more assessment. However, the pooled estimate for the effect of supervised exercise on fatigue has not been established yet. This study aims to determine the pooled effect of supervised exercise on fatigue in prostate cancer patients receiving ADT.

Methods

A literature search was conducted from PubMed, Clinicaltrial, and Cochrane Library, published up to January 2020 following the PRISMA guideline. We screened RCTs with our inclusion criteria and assessed the quality using the tools provided by Cochrane. The primary outcome analyzed in this study was fatigue measured as Standardized Mean Difference (SMD) with 95% Confidence Intervals (CIs). Heterogeneity was assessed using the I2 test. Subgroup analysis was conducted to determine the difference in exercise duration (<12 weeks and >12 weeks), modality (aerobic, resistance, and combination), and the onset of ADT (initiation and long-term). All analysis was performed using STATA 16.

Results

A total of 7 RCTs comprising 455 patients reported the fatigue using the FACIT-Fatigue, EORTC QLQ-C30, and Schwartz Cancer Fatigue Scale. The included studies presented a low risk of bias. Supervised exercise showed an overall reduction on fatigue (SMD = 0.25, 95%CI 0.07-0.44, p = 0.01, I2 = 0%). The subgroup test results showed no significant difference between exercise duration (p = 0.4), modality (p = 0.67), and onset of ADT (p = 0.57). The Egger’s test results showed no indication of publication bias (p = 0.64).

Conclusions

Supervised exercise reduces fatigue in prostate cancer patients receiving ADT. The available data show that there is no difference between exercise duration and modality. Furthermore, our findings highlight the benefits of supervised exercise in the initiation of ADT for preventing toxicities as well as relieving adverse effects in long-term ADT.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

230P - Molecular profiling and clinical characteristics of Chinese patients with prostate cancer (ID 830)

Presentation Number
230P
Lecture Time
09:00 - 09:00
Speakers
  • Ranlu Liu (Tianjin, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Prostate cancer(Pca) is one of the most common types of cancer in men. Androgen deprivation therapy(ADT) is the main choice of Pca treatment. However, major investigations have focussed on caucasians population. Here, we intended to explore the molecular characteristics and clinical characteristics between localized and metastatic of Chinese Pca patients.

Methods

29 Pca patients with localized or metastatic tumor were enrolled. Somatic and germline mutations were identified via targeted next generation sequencing with Acornmed panel including 808 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA) and chromosomal rearrangements. Clinical data of the cohort was collected and analyzed.

Results

Median age was 68 yrs (range 53-80), 62% were classified as metastatic(M), and 17% had received one prior ADT drug. The most common somatic mutations were observed in TP53(24%), FOXA1(21%), CDK12(17%), AR(10%), KRAS(7%), PIK3CA(7%), SPOP(7%), PTCH1(7%), ATM(7%) and TSC2(3%) genes. Median tumor mutational burden (TMB) was 7 Mus/ Mb(1-22). Germline pathogenic or likely pathogenic mutations occurred 17% of Pca patients, 4/5 mutations were DNA damage response genes, and 4 patients had metastatic Pca. AR was shared by both localized and metastatic Pca (2 in ADT- and 1 in ADT+). Mutated CDK12 was only detected in patients without any history of ADT drug(3 in M- and 2 in M+). Interestingly, Tp53 mutations were only detected in metastatic Pca(7/18 M+). FOXA1 mutations were observed more frequently in patients with localized Pca(4/11M- versus 2/18 M+).

Conclusions

These findings show differences in the genomics alterations of metastatic and localized prostate cancer. Germline mutations are more likely to be detected in patients with advanced prostate cancer. Mutations in the TP53 gene are more common in advanced prostate cancer. Additional correlative analyses are ongoing.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Yang, H. Wang, F. Lou, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd., All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

231P - Phase II study of pembrolizumab in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC): Updated follow-up of cohorts (C) 1-3 from KEYNOTE-199 (ID 887)

Presentation Number
231P
Lecture Time
09:00 - 09:00
Speakers
  • Jeffrey C. Goh (Herston, QLD, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pembrolizumab monotherapy has shown antitumor activity and acceptable safety in patients with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel.

Methods

The KEYNOTE-199 phase II study (NCT02787005) enrolled patients with RECIST-measurable PD-L1+ disease, RECIST-measurable PD-L1 disease, and bone-predominant disease irrespective of PD-L1 status in C1, C2, and C3, respectively. Patients had prior treatment with ≥1 NHA and 1 or 2 chemotherapies, including docetaxel, and received pembrolizumab 200 mg Q3W for 35 cycles or until progression/toxicity. The primary end point was ORR per RECIST v1.1 by blinded independent central review. Key secondary end points were time to PSA progression, DCR, PSA response rate, rPFS, OS, DOR, and safety.

Results

In total, 258 patients were treated (C1: 133; C2: 67; C3: 58), of whom 6 completed therapy (C1: 4; C3: 2). The median (range) time from enrollment to data cutoff was 31.3 mo (26.7-34.7), 30.6 mo (28.0-34.1), and 32.6 mo (27.4-34.4) in C1, C2, and C3, respectively. In patients with measurable disease, ORR (95% CI) was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2, and 6 of 10 responders experienced DOR ≥18 mo (Table). Median time to PSA progression was 4 mo regardless of cohort (Table). Grade ≥3 treatment-related AEs (TRAEs) occurred in 16%, 15%, and 17% of patients in C1, C2, and C3, respectively (1 death in each cohort from a TRAE [C1: sepsis; C2: unknown; C3: immune-related pneumonitis]).

Efficacy outcomes

Cohort 1 Measurable, PD-L1+ n = 133 Cohort 2 Measurable, PD-L1 n = 67 Cohort 3 Bone Predominant n = 58
ORR per RECIST v1.1 per BICR, measurable disease, n/N (%) 8/133 (6) 2/67 (3)
CR, n/N (%) 3/133 (2) 0
PR, n/N (%) 5/133 (4) 2/67 (3)
DCR (CR + PR + SD or non-CR/non-PD ≥6 mo), n/N (%) 14/133 (11) 4/67 (6) 12/58 (21)
PSA response rate,a pts w/baseline PSA, n/N (%) 8/124 (6) 5/61 (8) 1/58 (2)
Median time to PSA progression, mo (95% CI) 4 (4-4) 4 (4-6) 4 (4-4)
Median rPFS per PCWG3-modified RECIST, mo (95% CI) 2 (2-2) 2 (2-3) 4 (2-4)
Median OS, mo (95% CI) 10 (6-12) 8 (6-10) 14 (11-18)
OS at 24 mo, % 22 16 21

a≥50% decrease from baseline.

Conclusions

In 3 cohorts of docetaxel and NHA-pretreated patients with RECIST-measurable or bone-predominant mCRPC, pembrolizumab monotherapy led to promising antitumor activity and disease control and was well tolerated. There was durable antitumor activity and disease control, with survival up to 24 mo.

Clinical trial identification

NCT02787005, June 1, 2016.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J.C.H. Goh: Shareholder/Stockholder/Stock options: Immutep Ltd.; Honoraria (self): MSD; Advisory/Consultancy: AstraZeneca, Tesaro, BMS; Speaker Bureau/Expert testimony: Ipsen; Travel/Accommodation/Expenses: AstraZeneca, Astellas. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofy-Genzyme, MSD, BMS, Merk-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Research grant/Funding (self): Roche, Jansen, Astellas, MSD, BMS, Merk-Serono, AstraZeneca, Beigene, VCN Biotech; Travel/Accommodation/Expenses: Roche, Astellas, Jansen. M. Gross-Goupil: Honoraria (self): Ipsen, Janssen, Astellas; Advisory/Consultancy: Astellas, Janssen, Ipsen, MSD; Research grant/Funding (self): MSD, BMS, Janssen, AstraZeneca, Pfizer, Roche; Travel/Accommodation/Expenses: Amgen, MSD, Roche, Pfizer, Sanofi. U.N. Vaishampayan: Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc. R. de Wit: Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck, Sanofi, Roche, Janssen, Clovis. T.V. Alanko: Honoraria (institution): Eli Lilly, Roche; Advisory/Consultancy: Bayer, BMS, Celgene, Eli Lilly, MSD, Nordic Drugs, Roche, Shire; Speaker Bureau/Expert testimony: Bayer, Servier; Travel/Accommodation/Expenses: BMS, Celgene, MSD, Roche, Shire. S. Fukasawa: Speaker Bureau/Expert testimony: Pfizer, Bristol-Myers Squibb, Ono Pharmaceutical, Janssen Pharmaceutical. S. Feyerabend: Advisory/Consultancy: AstraZeneca, Bayer; Travel/Accommodation/Expenses: Janssen. R. Berger: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD, BMS, AZ. H. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J.S. de Bono: Advisory/Consultancy: AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Genentech/Roche, Janssen Oncology, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, Bayer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, SlasoSmi; Research grant/Funding (institution): AstraZeneca, Genentech, Sanofi, Taiho Pharmaceuticals, Daiichi Sankyo, Merck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma, GlaxoSmithKline, Cellcentric, Celgene, Sierra Oncology, Bayer, MedImmune, Medication, Terumo, Astellas Pharma, G. E.S. Antonarakis: Research grant/Funding (self): Janssen, Sanofi, Dendreon, AstraZeneca Clovis, Merck, JohnsonJohnson, Genentech, Novartis, Bristol-Myers Squibb, Eli Lilly, Tokai, Celgene; Advisory/Consultancy: Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, Merck, Eli Lilly, Amgen, Bayer, GlaxoSmithKline; Licensing/Royalties: Qiagen. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

232P - Real-world data on metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: A regional experience (ID 572)

Presentation Number
232P
Lecture Time
09:00 - 09:00
Speakers
  • Rachel Raju (Melbourne, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Both abiraterone and enzalutamide have shown to improve overall survival (OS), progression-free survival (PFS) and PSA response in patients with metastatic castration-resistant prostate cancer (MCRPC) regardless of previous treatment with chemotherapy (COU-AA301, COU-AA302, AFFIRM and PREVAIL). The data regarding the impact of these treatments in regional health services is scarce. This study assessed the survival outcomes in MCRPC patients in a regional health service in Victoria with the use of abiraterone and enzalutamide.

Methods

This retrospective clinical audit included 75 patients with the diagnosis of MCRPC treated with either abiraterone or enzalutamide between the period of January 1 2014 to December 31 2019 at Goulburn Valley Health. Patients were divided into two groups based on whether they received abiraterone or enzalutamide, and stratified according to ECOG performance, Gleason score, burden of disease, presence of visceral metastases and use of previous chemotherapy. The primary end point was PSA response. The secondary outcomes were PSA PFS, radiographic PFS, and OS.

Results

37 patients received enzalutamide, and the other 38 received abiraterone. Only 20% of patients in either group had visceral metastases. 32% of patients receiving enzalutamide had a high burden of disease, compared to 53% receiving abiraterone. 38% of patients in the enzalutamide group and 53% in the abiraterone group had received prior chemotherapy. PSA response rates were higher in the enzalutamide group than abiraterone group (70.3% vs 37.8%). Both PSA and radiographic PFS were longer in the enzalutamide group than abiraterone group; 7 months vs 5 months for both end points. OS was also found to be longer in patients receiving Enzalutamide; 30 months compared to 13 months in patients receiving Abiraterone.

Conclusions

Both abiraterone and enzalutamide have shown to result in significant PSA response rates, as well as PFS and OS benefit in MCRPC patients in the real-world setting, as reflected in previous clinical trials. The difference in responses and survival benefit between the groups are probably impacted by the unbalanced burden of disease and proportion of prior chemotherapy use.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

233TiP - Pembrolizumab (pembro) or placebo added to docetaxel and prednisone/prednisolone for metastatic castration-resistant prostate cancer (mCRPC) previously treated with next-generation hormonal agents (NHAs): KEYNOTE-921 phase III study (ID 724)

Presentation Number
233TiP
Lecture Time
09:00 - 09:00
Speakers
  • Daniel P. Petrylak (New heaven, CT, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pembro is a humanized monoclonal antibody that binds to PD-1 and prevents interaction with its ligands, PD-L1 and PD-L2. In the KEYSTONE-365 phase Ib/II study (NCT02861573), pembro added to docetaxel + prednisone had antitumor activity for mCRPC after progression with abiraterone acetate/enzalutamide. The randomized, phase III KEYNOTE-921 study (NCT03834506) will be conducted to assess efficacy and safety of pembro vs placebo added to docetaxel + prednisone in patients with mCRPC whose disease progressed on NHAs and who have not received chemotherapy.

Trial design

Eligibility criteria include histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology; evidence of metastatic disease or PSA (PCWG3), soft tissue (RECIST v1.1), or bone (PCWG3) progression; prior treatment with 1 (but not more than 1) NHA (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive prostate cancer or CRPC (nonmetastatic or metastatic); ongoing androgen deprivation; and Eastern Cooperative Oncology Group performance status 0 or 1. Key exclusion criteria were prior treatment with docetaxel/other chemotherapy, therapeutic radiopharmaceutical agents, or other systemic therapies. Approximately 1000 enrolled patients will be randomly assigned 1:1 to receive pembro 200 mg or placebo Q3W (≤35 cycles) added to docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg PO BID (≤10 cycles) until disease progression, unacceptable toxicity, or withdrawal. Response will be assessed using PCWG3-modified RECIST v1.1 by blinded independent central review (BICR) by imaging (CT/MRI/bone) Q9W through week 54 and then Q12W. The coprimary end points are OS and rPFS; additional details are in the table

End points in KEYNOTE-921

Primary Secondary
OS TFST
rPFS per PCWG3-modified RECIST v1.1, as assessed by BICR Confirmed PSA response ratea
ORR and DOR per PCWG3-modified RECIST v1.1, assessed by BICR
Time to PSA progression
Time to first symptomatic skeletal-related event
Time to pain progression based on BPI (SF) item 3 and on opioid analgesic use based on the analgesic quantification algorithm score
Safety and tolerability

aDecrease of ≥50% from baseline, measured twice ≥3 weeks apart.

.

Clinical trial identification

NCT03834506, February 8, 2019.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

D.P. Petrylak: Advisory/Consultancy: Ada Cap (Advanced Accelerator Applications) Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Incyte, Janssen, Mirati, Monopteros, Pfizer, Pharmacyclics, Roche, Sea; Shareholder/Stockholder/Stock options, Sold 10/2019: Bellicum, Tyme; Research grant/Funding (institution), *Denotes study trials that have terminated: Ada Cap (Advanced Accelerator Applications), Agensys Inc, *Astellas, AstraZeneca, *Bayer, BioXcel Therapeutics, Bristol-Myers Squibb, Clovis Oncology, Eisai, *Eli Lilly, *Endocyte, Genentech, *Innocrin, MedImmune, Medivation, Merck, Mirati, *Novartis, Pfi. N.D. Shore: Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Dendreon, Ferring, Fergene, Janssen, Merck, MDxHealth, Myovant, Nymox, Pfizer, Sanofi-Genzyme, Tolmar; Speaker Bureau/Expert testimony: Bayer, Janssen, Pfizer, Astellas; Leadership role, Immediate Past President: LUGPA. R. Ratta: Advisory/Consultancy: Astellas. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofi-Genzyme, MSD, Bristol-Myers Squibb, Merk-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Research grant/Funding (self): Roche, Jansen, Astellas, MSD, Bristol-Myers Squibb, Merk-Serono, AstraZeneca, Beigene, VCN Biotech; Travel/Accommodation/Expenses: Roche, Astellas, Jansen. B. Li: Full/Part-time employment: MSD R&D (China) Co., Ltd. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. K. Fizazi: Advisory/Consultancy: Amgen, Janssen, Sanofi, Astellas, Orion, MSD, Bayer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO15 - Metastatic Prostate Cancer Mimicking a Rectal Cancer: A Case Report (ID 498)

Presentation Number
YO15
Lecture Time
09:00 - 09:00
Speakers
  • Alfredo V. Chua (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

This is a case report of a 50-year-old Filipino male, who presented with a 1-year history of constipation and an enlarging nontender left lateral neck mass, initially 2 x 2 centimeters in size. There were no reported lower urinary tract symptoms. Neck ultrasound was done showing multiple, coalescing complex foci in the left lateral neck area, the largest of which was 2.8 cm. Fine needle aspiration biopsy showed atypical epithelial cells. Weight loss, occasional hypogastric pain, continuous enlargement of the neck mass to 7 x 7.5 cm, and persistence of constipation prompted the patient to seek consult at our institution. Further work-up revealed metastatic prostatic adenocarcinoma. Abdominal computed tomography (CT) scan showed markedly enlarged lymph nodes in the retroperitoneum, dilated urinary collecting systems and ureters, a liver nodule, and lytic defects at T10 and L1 vertebrae. The prostate gland cannot be completely separated from a rectal mass. Colonoscopy showed a circumferential, nodular, friable, and edematous mass spanning 10 to 20 cm from the anal verge causing 70% partial obstruction of the lumen. Biopsy showed a poorly differentiated carcinoma positive for pancytokeratin and negative for CDX2, LCA, synaptophysin and chromogranin. Further immunohistochemistry studies were negative for CK7, CK20, TTF-1, and p63 but positive for NKX3.1 favoring the prostate gland as the primary site. Baseline prostate specific antigen (PSA) was >100.00 ng/ml.

The patient received docetaxel with prednisone, androgen deprivation therapy, and bone support therapy. After 1 month of treatment, there was drastic regression in the size of the neck mass to 4 x 4 cm. After 5 months of treatment, it further decreased to 1.5 x 2 cm in size. PSA taken after 5 months of treatment was 18.07 ng/ml. The patient is on regular follow-up in our institution and is continuing his treatment.

This case highlights the importance of considering a prostate malignancy in a male patient presenting with gastrointestinal symptoms and a neck mass even in the absence of lower urinary tract symptoms. Serum PSA, pathologic and immunohistochemistry testing are important to guide the clinician in making the correct diagnosis and treatment.

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e-Poster Display Session (ID 87) Poster Display

Gynaecological cancers (ID 1149)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

243P - Target sequencing of 508 genes in Chinese epithelial ovarian cancer patients (ID 797)

Presentation Number
243P
Lecture Time
09:00 - 09:00
Speakers
  • Li Lei (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Target sequencing of epithelial ovarian cancer (EOC) has been widely used in clinical to detect the status of BRCA1/2 and genes in homologous recombination repair (HRR) pathway.

Methods

In a prospective study, unselected 215 EOC patients underwent germline and somatic testing with a 25-gene panel, of which 147 patients received target sequencing of 508 genes in OseqT panel. The sensitivity to platinum-based chemotherapy, OS and PFS were explored in various mutation categories.

Results

In 215 patients. 57 (26.51%) patients carried BRCA1 (46, 21.4%) or BRCA2 (14, 6.5%) pathogenic or likely pathogenic variants,3 of them carried both BRCA1 and BRCA2 variants. BRCA1/2 pathogenic carriers had significantly superior PFS and OS than non-mutated group. Deleterious mutation in HRR and MMR related genes can be found in 70 (32.6%) and 3 (1.4%) patients. Among 147 patients using OseqT panel for sequencing, 103 (70.1%), 15 (10.2%), 8 (5.4%), and 15 (10.2%) patients carried mutations of TP53, BRCA1, BRCA2, and PIK3CA mutations. There are also 2, 2 and 3 patients carrying mutations of p.E542K, p.E545K and p.H1047R mutations in PIK3CA , respectively. Mutations in ARID1A (11 patients, 7.4%), NF1 (7, 4.7%) and PTEN (6, 4.1%) can also be detected. In 118 patients received MSI testing, 22 (18.6%) of them are microsatellite instability (MSI)-low.

Conclusions

While BRCA1/2 and HRR related gene is still the most important target for gene test of EOC patient. The high prevalence of other cancer related gene such as PIK3CA cannot be overlooked. Large panel containing more cancer related genes may provide extra suggestions for doctors.

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e-Poster Display Session (ID 87) Poster Display

244P - Optimization of early diagnostics of cervical intraepitelial neoplasies and cervical cancer (ID 921)

Presentation Number
244P
Lecture Time
09:00 - 09:00
Speakers
  • Zakhirova Nargiza (Fergana, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To evaluate the practical significance of the effectiveness of the modified coloring solution “CIN-DIAG” in the diagnosis of pathological changes of the cervix.

Methods

The modified CIN-DIAG coloring solution is a sterile cotton swab on a plastic stick in a plastic tube, and the coloring solution is in the cap of the tube. Appearance of the coloring solution: a clear brown liquid; The volume of the coloring solution is 2 ml ± 5%; the pH of the coloring solution is in the range of 4 to 7 units. Mechanism of action: after applying the staining solution to the epithelial tissue, in the presence of atypical cells, folic acid, via the folate receptors on the surface of these cells, quickly enters the cytoplasm, is oxidized by the active oxygen present in the cell, and the tampon stains at different intensities. Normal cells have a low content of active oxygen, so there is little expression of folic acid receptors on the surface of the cells and the tampon does not stain after the reaction.

Results

The study included 20 (100%) patients, of which: with CIN I - 5 (25%), CIN II - 3 (15%), CIN III - 4 (20%), patients with cervical cancer - 5 (25 %), with cervical erosion - 2 (10%) and 1 (5%) women with a visually unchanged cervix. The age of women ranged from 29 to 64 years, the average age was 40 ± 0.7 years (p>0,5). In case CIN1, the tampon was colored dark green, with CIN2 it was blue-green, with CIN3 it was blue, and with cervical cancer, it was dark gray and black. The results obtained fully met the requirements of the regulatory document, the sensitivity of the coloring solution was 98%, the specificity was 95%.

Conclusions

Thus, the modified CIN-DIAG coloring solution has the advantages of economy, affordability, low technical requirements, safety and non-invasiveness, as a result of which it can be successfully applied in remote regions of the country.

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e-Poster Display Session (ID 87) Poster Display

245P - Clinicopathological features including response to platinum-based chemotherapy in endometrial carcinomas involving SWI/SNF complex inactivation. (ID 565)

Presentation Number
245P
Lecture Time
09:00 - 09:00
Speakers
  • Izumi Tanimoto (Tokyo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Dedifferentiated endometrial carcinoma (DDEC) and undifferentiated endometrial carcinoma (UDEC) are uncommon but exhibit aggressive clinical courses. Recent studies reported the loss of expression of SMARCB1 (INI1), SMARCA4 (BRG1), or ARID1A and ARID1B, core or DNA-binding subunits of switch/sucrose non-fermenting (SWI/SNF) complex, resulted in inactivation of SWI/SNF complex that was related to dedifferentiation of endometrial carcinoma.

The efficacy of platinum-based chemotherapy that is standard care for differentiated endometrial carcinoma is still unknown for UDEC and DDEC.

Methods

Thirteen patients diagnosed with UDEC or DDEC at our institute between 1999 and 2019 were included in this retrospective study. Inactivation of SWI/SNF complex was defined as deficiencies in expression of either INI1, BRG1, or ARID1A and ARID1B. Mismatch repair (MMR) status was also confirmed by immunohistochemistry. We evaluated clinical features and outcome in UDEC and DDEC.

Results

The median age at diagnosis was 54 years (range, 47-61). 2/5/6 patients presented with stage I/III/IV disease, respectively. Loss of INI1/BRG1/ARID1A and ARID1B was observed in 1/5/8 patients. Of the 11 patients whose MMR status were evaluated, 9 (82%) were identified as MMR deficient. Two patients underwent surgery alone because of early stage. Three patients received platinum-based chemotherapy as adjuvant therapy, and none of them has relapsed. Of the 8 patients who were unresectable or incompletely resected, 3 patients received platinum-based chemotherapy (doxorubicin/cisplatin or paclitaxel/carboplatin), 4 patients did not due to poor PS, and 1 patient did other regimen. In patients with unresectable or incompletely resected disease with platinum-based chemotherapy, response rate (RR), median progression free survival, and median overall survival (mOS) were 100%, 9.1 months, and 18.6 months, respectively. In patients with unresectable or incompletely resected disease without platinum-based chemotherapy, mOS was 2.7 months.

Conclusions

Platinum-based chemotherapy showed high RR for UDEC and DDEC. We will report case presentation about a few cases with specific clinical courses.

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e-Poster Display Session (ID 87) Poster Display

246P - Impact of genetically predicted elevated concentrations of C-reactive protein on ovarian cancer risk: A Mendelian randomization study (ID 748)

Presentation Number
246P
Lecture Time
09:00 - 09:00
Speakers
  • Haoxin Peng (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

C-reactive protein (CRP) is the inflammation-responsible protein and a significant rise of the plasma concentration of CRP is pervasive in the progress of ovarian cancer. However, there are few studies that comprehensively evaluate the correlation between CRP concentrations and ovarian cancer and the causal effect remains unknown. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted CRP levels and ovarian cancer risk.

Methods

Utilizing 32 CRP-related single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association studies, we investigated the correlation between genetically predicted CRP and ovarian cancer risk using summary statistics from the Ovarian Cancer Association Consortium (25,509 cases and 40,941 controls). The Inverse variance weighted (IVW) method was applied to estimate the causality between genetically elevated CRP concentrations and ovarian cancer risk. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different histotypes of ovarian cancer were also conducted.

Results

An inverse association was observed between genetically predicted one-unit increase in the log-transformed CRP concentrations and ovarian cancer (OR = 0.93, 95%CI = 0.87-1.00 p = 0.047). When results were examined by histotypes, an inverse association was observed between genetically predicted one-unit increase in the log-transformed CRP concentrations and endometrioid ovarian cancer (OR = 0.80, 95%CI = 0.70-0.91 p = 0.001), low-grade serous ovarian cancer (OR = 0.70, 95%CI = 0.58-0.86 p = 0.001) and serous ovarian cancer (OR = 0.84, 95%CI = 0.74-0.96 p = 0.012). Additionally, the results demonstrated the absence of the horizontal pleiotropy.

Conclusions

MR findings provide evidence for a causal relationship between genetically predicted one-unit increase in the log-transformed CRP concentrations and reduced ovarian cancer risk, overall and among specific histotypes. Further studies are warranted to investigate the underlying mechanism.

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e-Poster Display Session (ID 87) Poster Display

247P - The role of p53 gene suppressor and bcl-2 oncoprotein in non-epithelial ovarian tumor prognosis determination among child and adolescent patients (ID 895)

Presentation Number
247P
Lecture Time
09:00 - 09:00
Speakers
  • Anvar T. Shukullaev (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To determine the p53 gene suppressor and bcl-2 oncoprotein forecast role in non-epithelial ovarian tumor prognosis among child and adolescent patients.

Methods

Our search is based on immunohistochemical method results of 35 patients with non-epithelial ovarian tumors at I-IV stages, which were diagnosed and treated in oncogynecology and children oncology departments .

Results

The analysis of immunohistochemical method results shows 7(20%) patients among which had been marked high expression bcl-2 oncoprotein, 11(31,4%) moderate express, 16(45,7%) low express. Analysis of p53 gene suppressor results shows 9(25,7%) patients among which had been marked high expression, 11(31,4%) moderate express, 15(42,8%) low express. The high correlation between bcl-2 expression level increases and fast tumor growth, and therefore incurability of oncologic process among of patients had been revealed. Also the high probability of tumor recurrence was noticed. In the high-positive p53 gene suppressor rate group took place aggressive current of tumor process and these patients had early recurrence and metastases, which demanded recurrent aggressive chemotherapy

Conclusions

p53 gene suppressor and bcl-2 oncoprotein expression in non-epithelial ovarian tumors among the child and adolescent patients is characterized with high and low rates, which enables to use this rate determination for given pathology currency prognosis identification.

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e-Poster Display Session (ID 87) Poster Display

248P - The effect of progesterone on ALA-based PDT efficacy in uterine sarcoma cells (ID 355)

Presentation Number
248P
Lecture Time
09:00 - 09:00
Speakers
  • Ellie S. Chu (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Photodynamic Therapy (PDT) is an FDA approved cancer treatment. Hexyl-ALA, one of the 5-aminolevulinic acid (ALA) derivatives, induces higher protoporphyrin IX (PpIX) accumulation in cancer cells through the disrupted heme pathway. Upon specific light activation with oxygen, reactive oxygen species will be released for cancer cell destruction. Studies also revealed that ALA induced higher PpIX accumulation with hormonal supplement. Uterine sarcoma is a hormonal dependent gynecological cancer. Addition of hormones with ALA-PDT might be a new therapeutic approach.

This study aimed to demonstrate the effect of progesterone on hexyl-ALA-PDT in uterine sarcoma cells; the in-depth mechanism related to heme pathway is yet to be explored.

Methods

The intracellular PpIX generation and the phototoxicity mediated by Hexyl-ALA-PDT with progesterone were determined by flow cytometry and MTT assay respectively in the proposed cells.

Results

The PpIX generation and accumulation induced by hexyl-ALA in the proposed cells were increased in 10% and 30% when supplemented with progesterone and with progesterone and ferrochelatase inhibitor respectively. The progesterone enhanced hexyl-ALA-PDT effect from lethal dose of 20 (LD20) to lethal dose of 60 (LD60) at 2J/cm2.

Conclusions

Progesterone significantly enhanced hexyl-ALA-PDT efficacy in uterine sarcoma cells. Progesterone might enhance the efficacy of Hexyl-ALA-PDT through the modulation of heme biosynthetic pathway; thus in-depth mechanistic studies of hormonal enhancement on Hexyl-ALA-PDT efficacy deserved to be explicit.

Acknowledgement

Hexyl-ALA was kindly provided by Photocure ASA. This study was fully supported by a grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (Project no.: UGC/FDS17/M06/19).

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e-Poster Display Session (ID 87) Poster Display

249P - A Retrospective Study on the Treatment Response of Locally Advanced Cervical Cancer Patients to Combination Chemoradiotherapy (ID 725)

Presentation Number
249P
Lecture Time
09:00 - 09:00
Speakers
  • Siti Nabihah Sahralidin (Bandar Seri Begawan, Brunei)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemoradiotherapy (CCRT) is the primary treatment strategy for locally advanced cervical cancer (LACC) patients. Since June 2016, Brunei patients with LACC have been treated locally. However, no treatment response has been evaluated. As the first attempt in Brunei, this study aims to assess the treatment response of patients with LACC to the completing CCRT performed locally.

Methods

A retrospective cohort study on LACC patients referred to The Brunei Cancer Centre (TBCC) who met the inclusion criteria and had CCRT within the period between June 2016 and December 2019. Data was collected from TBCC patient database. All statistical analyses were carried out using R Studio Version 1.1.463 on Windows 10 where Shapiro-Wilk, Fisher’s exact and Mann-Whitney test was used. Inclusion criteria was confirmed histological diagnosis of squamous or adenocarcinoma or mixed LACC from stages IB to IIIB whom had started or completed CCRT within the period between June 2016 and December 2019. DFS is calculated in months starting from the completion of brachytherapy until the end of the study. OS is calculated in months starting from the time of diagnosis until the end of the study. Research proposal was granted ethics approval by the joint PAPRSB IHS Research and Ethics Committee and Medical and Health Research and Ethics Committee, Ministry of Health of Brunei Darussalam.

Results

40 patients were evaluated for analysis with mean age of 46.80 ± 12.23 years. Majority of the patients had a tumor diameter of ≥5cm (52.5%) and initial stage of 2B (55%). 90% of patients were compliant to chemotherapy. After completion of CCRT, 85% of patients had tumor regression. Upon follow-up, 10 patients had relapse with majority having initial stage of 2B (60%), tumor diameter of ≥5cm (90%) and tumor grade of G3 (70%). A significant difference was observed between the living status of patients, tumor response and tumor diameter in relapse and non-relapse patients with P values of <0.001, 0.002 and 0.009, respectively. 6 patients passed away due to cancer mortality.

Conclusions

There was an overall satisfactory outcome, tolerance and compliance to CCRT. Patients in high-risk group had higher incidence of relapse and had poor prognosis.

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e-Poster Display Session (ID 87) Poster Display

250P - Health-related Quality of Life in Women with Cervical Cancer (ID 423)

Presentation Number
250P
Lecture Time
09:00 - 09:00
Speakers
  • Almagul S. Zhabagina (Semey, Kazakhstan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Treatment for cervical cancer can significantly affect a patient’s quality of life. The purpose of this research: to study the quality of life in patients with cervical cancer and to analyze the dependence of the quality of life indicators on radiation doses obtained when living in areas adjacent to the Semipalatinsk test site.

Methods

In this study, a survey was conducted of 20 patients (women aged 27 to 70 years, average age 52 years) who received chemoradiation therapy. The questionnaire to assess the quality of life, carried out after treatment, using the official versions of questionnaires EORTC QLQ-CX24. The QLQ-CX24 module includes functional and symptomatic scales. The assessment of individual radiation doses received while living in areas exposed to radioactive exposure was carried out in accordance with official guidelines.

Results

The results obtained for functional scales: overall quality of life 78.4 ± 15.2, body image 80.2 ± 15.3, sexual activity 20.4 ± 19.5, sexual satisfaction 52.4 ± 18.3, sexual/vaginal functioning 42.6 ± 19.8 points. For symptomatic scales: symptoms 15.6 ± 12.8, lymphadenoma 12.9 ± 15.4, peripheral neuropathy 23.9 ± 14.7, menopausal symptoms 33.3 ± 28.4, sexual anxiety 32.4 ± 22.5 points.

Individual radiation doses received by patients while living in radioactively contaminated territories range from 1.06 to 36.11 cSv. For the study group, the relationship between indicators of quality of life and individual radiation doses have not been established. It is impossible to unequivocally affirm the absence of this dependence due to the insufficient number and heterogeneity of the studied group in a number of parameters.

Conclusions

A sufficiently high scale value indicates the overall quality of life reflects a good level of functioning. The rather low levels of the scales of symptoms, lymphedema, peripheral neuropathy indicate the severity of this symptomatology during preventive exposure to PALS. For the study group, the relationship between indicators of quality of life and individual radiation doses have not been established.

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e-Poster Display Session (ID 87) Poster Display

251P - Tendency of morbidity and mortality in cervical cancer in the last 10 years in the Republic of Uzbekistan (ID 639)

Presentation Number
251P
Lecture Time
09:00 - 09:00
Speakers
  • Mirzagaleb N. Tillyashaykhov (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

According to data of Globocan 2018 year, 18.1 million of new cancer cases have been registered and more than half of these cases occur in the Asian continent. Moreover, among women, cervical cancer takes the 4th place in morbidity and mortality. In the Republic of Uzbekistan cervical cancer takes third place among all cancers. Thus, remaining one of the frequent oncogynecological pathology, cervical cancer is a serious public health problem both in the world and in Uzbekistan.

Methods

To analyze condition of morbidity and mortality of cervical cancer we studied the state report -Information on diseases of malignant neoplasms.

Results

The average age of patients with cervical cancer was 61.3 in 2009 y, and 58.3 in 2019y. In 2009 y, the incidence rate per 100,000 population was 4.6, and in 2019 y this indicator increased to 5.6. Moreover, the highest incidence rate per 100,000 population in 2009 was observed in the Republic of Karakalpakstan, Tashkent city, Namangan, Andijan and Khorezm regions with indicators of 7.3; 7.0; 6.3; 5.8 and 5.7 per 100,000 population respectively, and the lowest in Surkhandarya (2.2), Kashkadarya (2.8) and Jizzakh (3.2) regions. In comparison of 2019 y, the highest incidence rate per 100,000 population was in Tashkent, the Republic of Karakalpakstan, Namangan and Khorezm regions with indicators of 11.8; 7.3; 6.8 and 6.5, respectively, and the lowest was observed in Kashkadarya (4.3), Samarkand (3.7) and Surkhandarya (2.8) regions. According to mortality rates, it was showed that there was growth of this indicator from 2.0 per 100,000 population in 2009 y to 3.0 per 100,000 population in 2019 y. Relatively high mortality rate per 100,000 population in 2009 y was observed in Tashkent (4.2), Khorezm (3.4) and Tashkent (2.9) regions, and in 2019 in the Republic of Karakalpakistan, Namangan and Khorezm regions with indicators of 5.8; 5.1 and 4.8, respectively.

Conclusions

In conclusion it can be shown that cervical cancer has a tendency to increase both morbidity and mortality in the Republic of Uzbekistan. The increase in morbidity is due to the intensive work of primary medical care, implementation of modern diagnostic methods, creation and use of diagnostic and treatment standards, and screening programs.

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e-Poster Display Session (ID 87) Poster Display

253P - Non-Epithelial Tumours of Ovary, An Experience from Qatar (ID 936)

Presentation Number
253P
Lecture Time
09:00 - 09:00
Speakers
  • Ammar Madani (Doha, Qatar)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Nonepithelial ovarian cancers constitute about 10 % of all ovarian cancers. They are divided into sex-cord stromal tumours (SCST) and germ cell tumours (GCT). The Aim is to report the experience at National Centre for Cancer Care and Research (NCCCR) in Qatar.

Methods

This is a retrospective study reviewing records of all patients who presented with a histopathologically diagnosed ovarian SCST and GCT at NCCCR between January 2010 and December 2016. Clinical data including age, stage at diagnosis, histopathology, treatment modalities, disease recurrence and status at last follow up was extracted.

Results

A Total of 25 women with Non Epithelial Ovarian Tumours were identified. 13 women were diagnosed with Ovarian SCST. 12 had granulosa cell tumour , 1 with steroid cell tumour and none of them had Sertoli-Leydig cell tumor. Median age at presentation was 43 years (Range 16-58). 12 patients (92 %) had stage I and 1 patient (8 %) had Stage III. 9 patients had TAH + BSO . 4 patients had conservative surgery without hysterectomy. 2 patients received Adjuvant chemotherapy .4 patients had recurrence. The 5 years Overall Survival (OS) was 100% and the 5 years Event Free Survival (EFS) was 69% with P value of 0.02.

GCT was diagnosed in 12 women. The median age at presentation was 24 years (Range 16 – 44). 7 patients (59 %) had teratoma, 4 patients (33 %) had Dysgerminoma and 1 patient had Yolk sac tumour (8 %). 9 patients ( 75 % ) had Stage 1, 2 patients had Stage 2 ( 17 % ) and 1 patient ( 8 % ) had Stage 4 disease .6 patients ( 50 % ) underwent U/L Oopherectomy .5 patients ( 42 % ) underwent U/L salpingoOopherctomy and Chemotherapy( BEP ) .1 pt. ( 8 % ) with Stage IV disease received only chemotherapy. There was 1 recurrence in the Retroperitoneal LNs in patient with Stage 2 disease. 5 years OS was 100 % and 5 years EFS was 83 % with P value of 0.14.

Conclusions

Survival in our study of SCST was excellent with all patients alive and disease free at last follow up. We recommend Complete Surgery (TAH + BSO) particularly if high grade, Stage 1C and above or completed child bearing to minimize recurrence.

GCTs have very good prognosis in all stages and even in recurrence. Fertility Sparing Surgery is appropriate for all patients with Stage 1 and most of patients with Stage 2 disease who desire fertility preservation.

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e-Poster Display Session (ID 87) Poster Display

254TiP - ENGOT-cx11/KEYNOTE-A18: A Phase 3, Randomized, Double-Blind Study of Pembrolizumab With Chemoradiotherapy in Patients With High-Risk Locally Advanced Cervical Cancer (ID 657)

Presentation Number
254TiP
Lecture Time
09:00 - 09:00
Speakers
  • Domenica Lorusso (Rome, Italy)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

High-risk locally advanced cervical cancer has a poor prognosis, and most patients (pts) experience recurrence in 2 y. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab (pembro) may be enhanced by concurrent chemoradiotherapy (CRT). After the KEYNOTE-158 study, in which pembro had durable antitumor activity, pembro monotherapy was approved for pts with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase 3, randomized, placebo (pbo)-controlled study of pembro with concurrent CRT for the treatment of locally advanced cervical cancer.

Trial design

~980 pts with high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembro 200 mg Q3W + CRT then 15 cycles of pembro 400 mg Q6W or 5 cycles of pbo Q3W + CRT then 15 cycles of pbo Q6W. The CRT regimen includes 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy.

Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the pt has received 20 cycles of pembro (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs pbo (~2 y) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST version 1.1 by blinded independent central review and OS. Secondary endpoints are PFS at 2 y; OS at 3 y; CR at 12 wk; ORR; PFS and OS in PD-L1–positive pts; EORTC Quality of Life Questionnaire (QLQ)–Core 30 and Cervical Cancer Module (EORTC QLQ-CX24); and safety. Enrollment is ongoing in 30 countries.

Clinical trial identification

ClinicalTrials.gov identifier, NCT04221945; EudraCT number, 2019-003152-37

Editorial acknowledgement

Writing support was provided by Michael S. McNamara, MS, ICON plc (North Wales, PA, USA), and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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e-Poster Display Session (ID 87) Poster Display

Haematological malignancies (ID 1150)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

260P - A phase I study of copanlisib, a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor, in Chinese patients with relapsed indolent non-Hodgkin lymphoma (iNHL) (ID 182)

Presentation Number
260P
Lecture Time
09:00 - 09:00
Speakers
  • Yuqin Song (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Copanlisib is a novel, potent, i.v. pan-PI3K inhibitor with predominant activity against PI3K-α and PI3K-δ isoforms that has demonstrated robust anti-tumor efficacy in patients with iNHL and was approved by the FDA in September 2017. Here we report on the safety, tolerability, pharmacokinetics (PK), and efficacy of single-agent copanlisib in Chinese patients with relapsed iNHL (NCT03498430).

Methods

Patients with relapsed histologically confirmed iNHL received copanlisib 60 mg as a 1-h i.v. infusion on days 1, 8, and 15 of a 28-day cycle. Safety was monitored throughout the study. The efficacy variable was objective tumor response rate (ORR) per independent radiologic review (Cheson et al. J Clin Oncol 2007). Plasma copanlisib levels were measured for pharmacokinetic analysis.

Results

13 patients (11 with follicular lymphoma and 2 with marginal zone lymphoma) received treatment; 12 patients were evaluable for efficacy. Median age was 40 years (range 30-64). The most common treatment-emergent adverse events of worst grade 3 were transient hypertension in 7 patients (53.8%) and hyperglycemia in 6 patients (46.2%), with no grade 4 hyperglycemia or hypertension events. No grade 5 events were reported. Copanlisib PK exposures (maximum observed concentration and area under the concentration vs time curve after single-dose administration) were in range of those from previous studies of copanlisib in non-Chinese patients. The ORR was 50% (95% CI 21.1, 78.9), with 6 patients achieving a partial response and 6 patients with stable disease as best response. The disease control rate was 100% (95% CI 73.5, 100.0). The estimated median duration of response was to be 63 days (range 1-115, including censored values). The median duration of stable disease was 163 days (range 106-218, including censored values).

Conclusions

Copanlisib was well tolerated in Chinese patients with relapsed iNHL at the approved clinical dose of 60 mg, with PK profiles comparable to non-Chinese patients. The observed efficacy profile of copanlisib was in the range of overall response rates previously observed for copanlisib monotherapy.

Clinical trial identification

NCT03498430.

Editorial acknowledgement

Jack Adams, Complete HealthVizion, McCann Health Medical Communications.

Legal entity responsible for the study

Bayer HealthCare Co. Ltd.

Funding

Bayer HealthCare Co. Ltd.

Disclosure

Y. Niu, T. Li, J. Zhai: Full/Part-time employment: Bayer HealthCare Co. Ltd. G. Cisternas, F. Hiemeyer, S. Reschke: Full/Part-time employment: Bayer AG. F. Huang, J. Garcia-Vargas, B.H. Childs, A. Mehra, C. Granvil: Full/Part-time employment: Bayer HealthCare Pharmaceuthicals, Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

261P - Clinical outcomes of early-progressed follicular lymphoma in Korea: A multicenter, retrospective analysis (ID 790)

Presentation Number
261P
Lecture Time
09:00 - 09:00
Speakers
  • Jun Ho Yi (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

While the expected survival of patients with FL almost reaches that of the normal population, the outcomes of patients who experience early progression within 24 months, that is, POD24 is dismal. Unlike the West, FL is less frequent in Asia as it accounts about 10% of non-Hodgkin’s lymphoma. To define outcomes and treatment patterns FL patients who experienced POD24 in Korea, we performed a multicenter, retrospective analysis.

Methods

The inclusion criteria were as follows, 1) Histologically confirmed diagnosis of FL grade 1, 2, and 3A; 2) Documented POD24. The primary endpoint was OS from the first diagnosis of FL.

Results

Between 2007 to 2019, a total of 73 cases were eligible for analysis. Median age at diagnosis was 53 (range, 28 – 83). All patients were Asians. In terms of FLIPI-1 risk group, 14 (19.2%), 24 (32.9%), and 35 (47.9%) patients were categorized as low-, intermediate-, and high-risk group, respectively. Sixty-two patients (84.9%) had received rituximab as the induction treatment, and 11 patients (15.1%) had not. CVP was the most commonly used regimen (N=40), followed by CHOP (N = 26). Forty-four patients (60.3%) had received maintenance treatment with rituximab and 29 patients (39.7%) had not.

POD24 was documented after a median duration of 11.6 months. Rituximab wad administered in 19 patients, and platinum-based regimens (N = 23) were the most commonly used backbone treatment followed by bendamustine (N = 15) and fludarabine-based regimens (N = 12). PFS from the first progression was 23.7 months. The median OS was 128.9 mo, with the 5-year being 75.2%. OS did not significantly differ by the re-induction regimen, use of rituximab, or SCT.

When we compared these patients to our previous cohort in which 191 FL patients without POD24 were included, the 5-year survival rate was significantly inferior in the current cohort (75.2% vs. 95.7%, p < 0.001).

Conclusions

The 5-year OS rate of our patients with POD24 seems better than Western data, although there are many confounding factors including baseline FLIPI and the induction treatment. As expected, the 5-year OS rate of patient with POD24 was inferior to that of patients without POD24. To best salvage these patients, further studies are warranted to develop effective treatment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

262P - Correlation between phosphorylated pI3K expression, phosphorylated AKT, and phosphorylated MTOR with serum dehydrogenase lactate level in non-Hodgkin lymphoma (ID 384)

Presentation Number
262P
Lecture Time
09:00 - 09:00
Speakers
  • Hary Gustian (Bandung, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

There are 5,7 male and 3,8 female Non Hodgkin Lymphoma (NHL) patients per 100,000 populations in Indonesia. The expression of pPI3K/pAKT/pMTOR is an important expression in patients with NHL. Cascade signals from these biomarkers lead to translational regulation, cell survival, cytoskeleton organization, and ion transport. Lactate dehydrogenase (LDH) is an important marker in patients with NHL. pPI3K/pAKT/pMTOR increases gene transcription and encourages LDH proliferation.

Methods

An observational study by observing and measuring cancer cell samples from patients. Data collection method is cross sectional in which the independent and dependent variables are examined simultaneously. The expression values of pPI3K, pAKT, and pMTOR are expressed in form of histoscore. There are three range of intensity values which are one means weak, two means medium, and three mean strong, while the four distribution range are one means <20%, two means 20-50%, three means 50-80%, and four means >80%. Therefore the possible range of histoscore is from 1 to 12.

Results

The mean phosphorylated PI3K expression in NHL patients is 5,29 (2,95). The mean phosphorylated AKT expression in NHL patients is 4,71 (2,26). The mean expression of phosphorylated MTOR in NHL patients is 7,62 (1,86). The mean serum LDH level NHL patients is 428,57 (139,63) IU/L.

Conclusions

Correlation between the average expressions of pPI3K with the average level of serum LDH in NHL patients is relatively weak. The correlation between the mean of PAKT expression and the average level of LDH serum in NHL patients is classified as very weak. The correlation between mean pMTOR expression and mean serum LDH levels in NHL patients is very weak.

Legal entity responsible for the study

Andalas University, Padang.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

263P - Good response to chemotherapy in primary CNS lymphoma may not translate into significant neurocognitive improvement in comatose patients (ID 625)

Presentation Number
263P
Lecture Time
09:00 - 09:00
Speakers
  • Ryan M. Lim (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Primary Central Nervous System Lymphoma (PCNSL) is a rare type of non-Hodgkin’s lymphoma that tends to occur in the elderly and immunocompromised patients. The mainstay of treatment is that of high-dose methotrexate-based chemotherapy. Studies suggest that radiological response to high-dose methotrexate-based chemotherapy correlates with an improvement in neurocognitive ability that remains stable on follow-up. However, no studies involving patients with extremely poor neurological status prior to the commencement of chemotherapy have been reported, and the neurological prognosis of this group of patients remains unknown.

Methods

We describe 3 patients with biopsy-proven PCNSL that had comatose neurological states (Glasgow Coma Scale, GCS of 3-5) as a result of disease progression prior to treatment. The patients all experienced a drop in GCS in the short time frame between initial presentation and the start of treatment ranging from 12 days to 6 months.

Results

Case 1 initially presented with lethargy, drowsiness and behavioural change, with disease foci in a periventricular distribution. Case 2 presented with diplopia and poor visual acuity, as a result of disease affecting the optic chiasma and brainstem. Finally, case 3 had unsteady gait, memory impairment and slow speech at diagnosis, with disease over periventricular regions involving the corpus callosum and corona radiata. All were treated with high-dose methotrexate-based chemotherapy. However, although excellent radiological responses to treatment were achieved, no meaningful neurological or cognitive recovery was documented.

Conclusions

PCNSL patients with a baseline comatose state have poor neurological prognosis even if there is excellent tumour response to chemotherapy. As it is an aggressive disease with an unpredictable clinical course, rapid detection and prompt treatment is crucial in this disease entity.

Legal entity responsible for the study

National Cancer Centre Singapore.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

264P - Treatment outcome of primary testicular lymphoma patients treated in tertiary care centre in Chennai (ID 557)

Presentation Number
264P
Lecture Time
09:00 - 09:00
Speakers
  • Sivasubramaniam Kumaravelu (Chennai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lymphomas are the most common testicular malignancy in elderly male with DLBCL being most common subtype. Less common histological subtypes include Burkitt lymphoma and follicular lymphoma. Testicular DLBCL has poor treatment outcomes than nodal DLBCL due to high risk of relapse in opposite testes, CNS and other sites.

Methods

From the database, patients diagnosed as testicular lymphoma over a period of five years from January 2013 to December 2017 at department of Madras Medical College, Chennai were retrieved and analysed.

Results

8 patients were found to have testicular lymphoma with all being DLBCL subtype. Median age of diagnosis was 61 years. 25% (n=2) patients had B symptoms. 4 patients had stage IE, 2 patients had stage II and 2 patients had stage IV. LDH was elevated in stage IV patients. None developed contralateral testicular lymphoma. All patients underwent high inguinal orchidectomy of involved testis. 3 patients had removal of opposite testis after completion of whole treatment and 5 patients received radiotherapy of 30Gy to contralateral testes. All patients received R-CHOP once in 21 days for 6 cycles along with intrathecal methotrexate of 12.5mg except 1 patient receiving 4 cycles only due to poor PS. 2 patients had febrile neutropenia during chemotherapy and got recovered. 2.5 year DFS was 62.5%(n=5) and 2.5 year OS was 75%(n=6) with a median follow up period of 56 months.

Conclusions

Due to rarity of this tumour standard treatment regimen remains unknown. R-CHOP gives treatment outcomes comparable to the literature.

Legal entity responsible for the study

Sivasubramaniam.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Head and neck cancer, excluding thyroid (ID 1152)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

271P - Cost-effectiveness of pembrolizumab as monotherapy or in combination with chemotherapy versus EXTREME regimen for the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma in Taiwan (ID 753)

Presentation Number
271P
Lecture Time
09:00 - 09:00
Speakers
  • Cheng Hsu Wang (Keelung, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To assess the cost-effectiveness of pembrolizumab monotherapy (P) for CPS ≥1 subpopulation and in combination with platinum+5-FU chemotherapy (P+C) for the overall population versus cetuximab+platinum+5-FU chemotherapy (EXTREME regimen: E) for the first line treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in Taiwan.

Methods

A cohort-based partitioned survival model consisting of three health states (progression-free, progressed disease, and death) was developed. Using overall survival and progression free survival data from the P and P+C vs E arms of the KEYNOTE-048 study, the proportion of patients in each health state was estimated by parametric modeling over a 10-year period. Healthcare resource utilization data and costs per unit were sourced from the Taiwan National Healthcare Insurance Research Database, Cancer Registry database based on Taiwan National Health Insurance Administration (NHIA) reimbursement prices.

Results

In the base case analysis, P and P+C resulted in higher costs vs E (P: $1,964,859 vs E: $1,200,788 in the CPS ≥1 population; P+C: $2,301,474 vs E: $1,236,156 in the overall population), and higher quality adjusted life years (QALYs: P:1.22 vs 0.73 in the CPS ≥1 population; P+C: 1.30 vs 0.74 in the overall population). The incremental cost effectiveness ratio (ICER) for P vs E was NT$1,571,914/QALY in the CPS ≥1 population, and NT$1,912,195/QALY for P+C vs E in the overall population, respectively. At a willingness-to-pay threshold of 3 times Taiwan per capita Gross Domestic Product (GDP: NT$2,309,934), the resultant incremental cost/QALY for both P and P+C are considered cost-effective.

Conclusions

Both P and P+C are projected to be cost-effective options compared with E for the first-line treatment of R/M HNSCC patients. These results reflect the assumption of the publicly known pembrolizumab price in Taiwan; the price under managed entry agreement with NHIA may result in lower ICERs further demonstrating greater cost-effectiveness value.

Legal entity responsible for the study

MSD LLC Taiwan Branch, Taiwan.

Funding

MSD LLC Taiwan Branch, Taiwan.

Disclosure

C.H. Wang: Advisory/Consultancy: Merck Sharp & Dohme (I.A.) LLC Taiwan Branch. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

272P - Early metabolic changes in PET metrics over initial 8 weeks of treatment in patients with advanced head neck squamous cell carcinomas treated with chemotherapy (ID 675)

Presentation Number
272P
Lecture Time
09:00 - 09:00
Speakers
  • Ashish M. Vaidya (Nagpur, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Head and neck cancer is the most common cancer in India and the 6th most common malignant tumour worldwide. Around 60% of patients are diagnosed in advanced stage.No biomarker is available to assess the chemotherapy response. How early to assess it is not establised. So, it is of paramount to integrate molecular imaging into precision oncology care, exploring the potential of imaging as a biomarker.

Methods

We conducted a prospective observational study at NCI,Nagpur,India; during 2019.The 102 advanced cases of SCC Head neck region were enrolled in study after ISC approval and informed consent.All patient’s history,addictions,clinical examination were noted. Chemotherapy: Docetaxel-Cisplatin-5FU or Paclitaxel-Carboplatin.Imaging:Baseline PET-CT scans were done followed by response evaluation scan at 2 weeks interval.The pattern of PET metrics Tumour-SUVmax and Nodal-SUVmax analysed using PERCIST criteria. P<0.05 was considered statistically significant.

Results

The mean age of study population was 48.96 yrs with male preponderance 70 (89.74%) males. The most common site involved were Buccal mucosa in 31 (39.74%) followed by tongue 20(25.64%). The 64 (82.05%) were tobacco chewer, 17 (21.79%) alcoholic and 21(26.92%) were smokers,all were in advanced stage, 6 (7.69%) stage III, 72(92%) in stage IV. The average(SD) PET-CT SUVmax value of the primary tumour during baseline, first, second and third response evaluation were 16.17(6.03), 12.53(4.94),11.38(5.47) and 12.64(7.57) respectively.As compared to baseline the change/decrease in PET-CT SUVmax values during subsequent response evaluation at 2weeks interval during chemotherapy for primary tumour and regional lymph node were statistically significant with p<0.00001.

Conclusions

PET-CT metrics SUVmax detects metabolic response in the primary tumour and regional lymph nodes in advance head and neck squamous cell carcinoma during chemotherapy as early as 2 week with clinical corelation. It has a potential role as surrogate marker for treatment response evaluation and tailoring of the management of squamous cell carcinoma of head neck region.

Legal entity responsible for the study

National Cancer Institute, Nagpur, India.

Funding

National Cancer Institute, Nagpur, India.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

273P - Long term outcomes of locally advanced & borderline resectable esthesioneuroblastoma and sinonasal tumour with neuroendocrine differentiation treated with neoadjuvant chemotherapy (ID 146)

Presentation Number
273P
Lecture Time
09:00 - 09:00
Speakers
  • Vikas Talreja (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The present analysis was done to estimate the 5-year outcomes and late adverse events of locally advanced sinonasal tumours treated with induction chemotherapy followed by local therapy.

Methods

Twenty-five patients with locally advanced esthesioneuroblastoma or sinonasal neuroendocrine tumours treated between August 2010 to August 2014 with induction chemotherapy followed by local therapy were selected. The 5-year outcome and late adverse events (CTCAE version 4.02) were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. COX regression analysis was used to identify factors impacting PFS and OS.

Results

The median follow-up was 5.15 years. The 5 year PFS in esthesioneuroblastoma cohort and in SNEC cohort was 63.5 %( 95%CI 28.9-84.7) and 34.6 % (95%CI 10.1-61.1) respectively (P=0.1). The only factor impacting PFS on multivariate analysis was a response to neoadjuvant chemotherapy (p=0.033). The 5 year OS in esthesioneuroblastoma cohort and in SNEC cohort were 91.7% (95%CI 53.9-98.9) and 46.2% (95%CI 19.2-69.6) respectively (p=0.024). Any grade late adverse event was seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%).

Conclusions

Neoadjuvant chemotherapy in advanced sinonasal cancers is associated with improvement in 5-year outcomes. However, late side effects especially metabolic are seen in these patients and should be evaluated during follow up.

Legal entity responsible for the study

Tata Memorial Hospital.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

274P - Comparing comorbidity indices in predicting 90-day mortality after radical radiotherapy for head and neck cancer (ID 744)

Presentation Number
274P
Lecture Time
09:00 - 09:00
Speakers
  • Therese Y. Tsui (Hong Kong, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Treatment of head and neck cancer (HNC) is associated with significant acute toxicity, and accurately identifying patients who will not tolerate aggressive treatment remains a challenge. Comorbidity indices are known prognostic factors for HNC survival outcomes. However, no index has been found to be superior, and their performance in predicting early outcomes in HNC patients is not known. This retrospective analysis aims to determine the role of comorbidity indices in predicting 90-day mortality after radical radiotherapy.

Methods

Study population included all non-thyroid, non-metastatic HNC patients who received curative intent radiotherapy, with or without chemotherapy, from 2016-2019 in a single tertiary oncology centre. 260 patients were randomly selected for model building and comparison. Multiple logistic regression was used to analyse the performance of six comorbidity scores – the Charlson Comorbidity Index (CCI), age-adjusted CCI (ACCI), head and neck CCI (HNCCI), Simplified Comorbidity Score (SCS), Adult Comorbidity Evaluation-27 (ACE-27) and the Washington University Head and Neck Comorbidity Index (WUNHCI)– in predicting risk of 90-day mortality after radical treatment. ROC analysis was done to identify the best performing index, on which further analysis was carried out to determine the best cut-off.

Results

46 out of a total of 958 eligible patients (4.8%) died within 90 days after radical treatment in our cohort. Four of the six comorbidity scores were independent predictors of early mortality [CCI: odds ratio (OR) 1.298, p=0.004; ACE-27: OR 2.577, p<0.001; ACCI: OR 1.324, p<0.001; HNCCI: OR 2.056, p=0.001]. From ROC analysis of the remaining four comorbidity indices, ACCI was the best performing model (AUC 0.728). Calculation of the Youden Index yielded a threshold of ACCI score > 3 as the most discriminatory cut-off in predicting 90-day mortality. ACCI >3 was associated with more than 20% mortality in our cohort.

Conclusions

Age-adjusted CCI > 3 is associated with a higher risk of early mortality in HNC patients after radical radiotherapy. This may be taken as an easily accessible reference for discussion in the clinical setting.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

275P - Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: A double institution retrospective analysis from India (ID 795)

Presentation Number
275P
Lecture Time
09:00 - 09:00
Speakers
  • Vivek Agarwala (Howrah, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

First-line TP-Ex-like regimen (taxane-platinum-cetuximab) in recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) followed by 2nd-line immunotherapy represents one of the standards of care. We report our experience from 2 tertiary care institutions of India.

Methods

This is a retrospective analysis of 54 consecutive patients of platinum-sensitive R/M SCCHN treated between August 2017 and May 2020 with 1st-line weekly combination paclitaxel 80mg/m2, carboplatin AUC2 and cetuximab 400mg/m2 loading followed by 250mg/m2 (PCC) for upto maximum 12 weeks. Non-progressive patients were then started on cetuximab maintenance. Patients were further treated with 2nd-line nivolumab or oral metronomic chemotherapy (OMCT) on progression as per feasibility. Overall Response rates (ORR), progression-free survival 1 and 2 (PFS-1 & PFS-2), overall survival (OS) and safety were evaluated.

Results

The median age of the study population was 56.5 years with 48 males; 30/24 had oral/non-oral primaries; ECOG PS was 1/2 in 32/22 cases; 50 patients had local disease while 34 had distant metastasis; 41 had history of tobacco abuse; 7/6 patients had renal/cardiac dysfunction respectively. The ORR and median PFS-1 was 79.7% and 7.031 months respectively. Out of the 33 patients who progressed, 19/10/4 received 2nd-line nivolumab, OMCT or best supportive care respectively. The ORR to 2nd-line nivolumab / OMCT was 36.8%/10% and the median PFS-2 was 6.5 / 2 months respectively. The median OS of the entire cohort was 15.014 months while that of the selected 2nd-line nivolumab cohort was 20.4 months. Grade III/IV adverse events on 1st-line therapy included neutropenia (31.4%), anemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%) and skin reaction (16.6%) and there were no grade III/IV treatment related toxicities in 2nd-line.

Conclusions

First-line weekly PCC is an effective regimen for palliative therapy of platinum-sensitive R/M SCCHN with acceptable toxicity profile. Addition of 2nd-line nivolumab on progression further improves the outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

276P - Sarcopenia to predict overall survival in head and neck cancer patients receiving chemotherapy: A systematic review and meta-analysis (ID 524)

Presentation Number
276P
Lecture Time
09:00 - 09:00
Speakers
  • Felix Kwenandar (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Head and neck cancer (HNC) was the seventh most common cancer worldwide in 2018. As much as 330,000 people die annually from HNC. Sarcopenia as a result of chemotherapy toxicity or other factors is ubiquitous in HNC patients. This meta-analysis aims to analyze the significance of sarcopenia to predict overall survival in HNC patients receiving chemotherapy.

Methods

A systematic review was performed according to PRISMA guidelines. A literature search was conducted by three independent reviewers on all of the studies that include sarcopenia in HNC patients undergoing chemotherapy using PubMed and PubMed central databases. The outcome of interest in this study is the overall survival. Data synthesis and statistical analysis were carried out using Review Manager Software.

Results

A total of 5 studies including 1,088 HNC patients undergoing chemotherapy met the inclusion criteria for this meta-analysis. All studies included were observational studies. This meta-analysis uncovered that there is a significant correlation between the existence of sarcopenia and overall survival in HNC patients receiving chemotherapy (HR 1.50; 95% CI 1.15-1.95; P< 0.003). The quality of the studies was assessed with the Newcastle Ottawa Scale (NOS) shows “good” quality in all included studies.

Conclusions

Our meta-analysis shows that the presence of sarcopenia predicts worse overall survival of HNC patients undergoing chemotherapy. This finding can be used by physicians to improve the assessment of risk and benefit of initiating or continuing chemotherapy in these patients. Further study needs to evaluate in better patient selection and adjusting the confounder.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

278P - Serial assessment of parotid volume changes during radical chemoradiation of locally advanced head and neck cancer: Its implications in practice of adaptive radiotherapy (ID 927)

Presentation Number
278P
Lecture Time
09:00 - 09:00
Speakers
  • Aathira T. T S (Rishikesh, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Radical chemoradiation (CTRT) is the standard of care in locally advanced head and neck cancer (LAHNC). For mitigating the normal tissue toxicity, many techniques have been explored and utilized, including IMRT and adaptive radiotherapy (ART). Significant anatomical variations occur during CTRT due to weight loss and tumor and normal tissue changes. In the present study, serial changes in parotid volumes were assessed with weekly scans along with dosimetric correlation.

Methods

This prospective, single-institutional study, included 12 patients with LA HNC receiving CTRT. All underwent CT simulation (CT sim) followed by weekly rescans from week 1 to 6. Target volumes and organs at risk, including right & left parotids (RP & LP) were recontoured in all rescans after fusion with the CT sim. Dose overlay was done in each rescan to generate a hybrid plan to study corresponding dosimetric variations. Volume changes in parotids were reported as percentage change from the baseline.

Results

In CT sim, right parotid volumes (RPV) ranged from 15.7 - 44.2 cc (mean - 24.1 SD – 7.9) and left parotid volume (LPV) from 12.2 - 47.1 cm3 (mean 22.8, SD -9.9). Mean % reduction in RPV in week 1, 2, 3, 4, 5 and 6 were 14.2% (p=0.003), 17.1% (p=0.007), 21.8% (p < 0.001), 25.6% (p < 0.001), 30% (p < 0.001), 32.1% (p < 0.001) respectively. Mean % reduction in LPV in week 1, 2, 3, 4, 5 and 6 were 8.9% (p=0.016), 14.5% (p=0.012), 17.7% (p=0.001), 20.1% (p=0.002), 24.9% (p < 0.001), 28.9% (p < 0.001) respectively. LP D mean showed a significant increase in week 3 (4.6% from baseline, p=0.019) and week 6 (7.6% from baseline, p=0.034). Both parotids showed a significant reduction in V26 Gy with 12.3%, 15.1%, 18.9%, 22.9%, 25.7%, 27.0%, respectively, from week 1 to 6 in RP and 7.3%, 15.7%, 13.8%, 16.8%, 20.8%, 24.1%, respectively, in LP.

Conclusions

Parotid volume shrinkage started from the 1st week. At the end of CTRT, there was 30-32% reduction in volume. V26 Gy of both parotids showed significant reduction during CTRT. Studies focusing on parotid volume changes shows wide variations in volume reduction ranging from 13% to 50% at the end of treatment. These parotid volume changes during RT need to be incorporated while doing ART in LAHNC.

Legal entity responsible for the study

Uttarakhand.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

279P - Clinico pathological characteristics and survival outcome in oral cavity cancer with masticator space involvement (T4b): A retrospective single institutional experience (ID 244)

Presentation Number
279P
Lecture Time
09:00 - 09:00
Speakers
  • Abdulla Kunnummal Palathinkara (Thiruvananthapuram, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Oral cavity cancer with the masticator space involvement is considered as very advanced localised disease and staged as T4b in AJCC 8th edition, along with the involvement carotid artery, base of skull or prevertebral fascia. NCCN treatment guidelines consider this as inoperable disease and advocate non-surgical options or palliative treatment. This study intends to compare the different treatment modalities in T4b oral cavity cancer and their impact on survival.

Methods

This is a retrospective study of 150 patients with T4b oral cavity cancer, from 2013 to 2015 and follow up data till 31st July 2019 were collected. All patients had biopsy-proven SCC and CT evidence of masticator space involvement.

Results

Total of 150 patients were included. 102 patients had received curative treatment and 48 patients had received palliative treatment. 30% in the curative group and 42% in the palliative group were supra notch disease. In the curative group 84% were treated with surgery and adjuvant treatment, and the remaining had received RT with or without chemotherapy. 90% patients in the surgically treated group had attained margin negative resection. 4-year OS in the curatively treated group was 58.9% and in the palliative group was 12%. 2-year OS was 69% and 31% respectively, (p=0.001). The survival of supra notch disease was not different from infra notch disease either in the curative group (61% v/s 57%, p=0.452) or in the palliative group (10% v/s 14%, p=0.13). The surgically treated patients in the curative arm had significant survival advantage over the patients who had received only RT with or without chemotherapy, (63.5% v/s 34%, p=0.001).

Conclusions

Curatively treated oral cavity cancer with masticator space involvement has good survival outcome. Clinicopathological spectrum of supra notch disease is not different from infra notch disease, and their prognosis is similar to infra notch disease, if margin-negative resection is attained. Radical intent treatment, preferably surgery should be offered to all patients with masticator space involvement, if negative margin is anticipated from preoperative imaging.

Legal entity responsible for the study

Director, RCC, Trivandrum.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

280P - Safety and efficacy of concurrent chemoradiotherapy for head and neck cancers in younger versus older patients: Post hoc analysis of a randomized control trial (ID 555)

Presentation Number
280P
Lecture Time
09:00 - 09:00
Speakers
  • Vanita Noronha (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is a well-known malignancy in the older population. However, there is scarcity of data on the effect of chemoradiation on them. We did a posthoc analysis of a randomized study conducted at our institution to understand this effect.

Methods

We did a posthoc analysis of the study where the patients received chemoradiation. The database of this study was used for the present analysis. We evaluated the differences in demography, grade 3 or worse adverse events, compliance of treatment, loco-regional control (LRC), progression free survival (PFS) and overall survival (OS) between older (≥ 60 years) and the younger patients.

Results

Out of 300 patients, 283 (94.3%) comprised the younger cohort (age < 60 years) while the older cohort included 17 (5.7%) patients. There was no difference in the occurrence of severe (grade 3/4) toxicities in the older cohort when compared to the younger patients. At a median follow up period of 22 months (range, 3-51), the cumulative LRC at 2 years was 67.1% and 100% in younger and the older group respectively (P = 0.018). The estimated median PFS in younger patients was 24.4 months (95% CI, 12.5 to 36.3), while it was not reached in the older group (P = 0.53). The estimated median OS was 41.3 months in the younger and not reached in the older group (P = 0.613).

Conclusions

Older patients with locally advanced HNSCC who received radical concurrent cisplatin-based chemoradiotherapy showed significantly better LRC. Older patients experienced similar adverse events as compared to the younger ones.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

281P - Prevalence of premalignant lesions and oral cancer among tobacco-using tea plantation workers of Nilgiri Hills, Tamilnadu, India (ID 138)

Presentation Number
281P
Lecture Time
09:00 - 09:00
Speakers
  • Delfin Lovelina Francis (Chennai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tea industry is one of the oldest industries in India. In India the four main tea-producing states are Assam, West Bengal, Kerala and Tamil Nadu. Tea is also grown in parts of Tripura and Himachal Pradesh. There are more than one million workers in the tea industry in India comprising mainly of scheduled castes, tribes and ethnic minorities. Poor socio-economic conditions, ignorance due to illiteracy, over-crowded and unhygienic living conditions in the residential colonies make tea garden population vulnerable to various communicable diseases and malnutrition. This study was contemplated with an aim to assess the tobacco use and prevalence of premalignant lesions and oral cancer among tea plantation workers, Nilgiri Hills, Tamil Nadu, India.

Methods

A cross-sectional descriptive study was conducted to assess the tobacco use pattern, its frequency and type. Individual oral examination was done by a single examiner to check the premalignant lesions and oral cancer among tea plantation workers, Nilgiri Hills. Data was collected using a pretested Questionnaire, which included Demographic data, tobacco habits, its frequency and form. The data collected was analysed using SPSS version15.

Results

showed that among 400 study population from 5 tea estates, 46% had no formal education and 65% had indigenous brushing habits. 52% of oral mucosal lesions were detected, out of which most commonest was leukoplakia 34%, 42% tobacco pouch keratosis and 6% malignant oral tumours. Prevalence of oral mucosal lesions in the study population was due to tobacco usage and lack of awareness regarding the deleterious effects of the products used.

Conclusions

Tobacco use is a major preventable cause of premature deaths and diseases, the dangers from smoking and chewing tobacco are well documented within the literature but the public’s lack of knowledge of the risks is a concern. Health professionals are encouraged to ensure that the public is made aware of these risks.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

282P - Filipino head and neck cancer patients and their quality of life (ID 194)

Presentation Number
282P
Lecture Time
09:00 - 09:00
Speakers
  • Frederic Ivan L. Ting (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In the management of head and neck cancer (HNC), assessment of quality of life (QoL) is imperative because of the potentially debilitating effect of treatment toxicities. Currently, there are no published data assessing the QoL in Filipino HNC patients, thus this study.

Methods

This cross-sectional study utilized the University of the Philippines - Department of Health Quality of Life scale. Patients with head and neck cancers at the University of the Philippines - Philippine General Hospital from February to September 2019 were invited to participate.

Results

A total of 418 patients were included in the study with a mean age of 42 years old (range 18 to 73 years old). In general, Filipino head and neck cancer patients had moderate QoL (mean score of 4.59±0.79). All of the QoL domains (physical, emotional, cognitive, and related functions) had a score of 3-5 (moderate), except for the social status domain which had a mean score of 5.51±0.83 (high). Among socio-demographic factors, patients who are employed and with additional funding sources on top of their income have better global QoL (p<0.01). Clinically, patients with higher stages of disease, fungating tumors, post-laryngectomy, have a feeding tube, with a tracheostomy, and had chemotherapy have lower global QoL (p<0.01).

Conclusions

Filipino patients with head and neck cancers have an overall moderate quality of life, with high scores in the social domain. Patients with higher tumor burdens and have been exposed to chemotherapy have lower QoL scores, while patients with financial stability and aid have better QoL scores.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

283P - Descriptive epidemiology of head and neck cancer in Niger: First results from the National Cancer Registry (ID 228)

Presentation Number
283P
Lecture Time
09:00 - 09:00
Speakers
  • Salamatou Mamoudou Garba (Niamey, Niger)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Worldwide, there are approximately 560 000 new cases diagnosed with head and neck cancer and 300 000 deaths each year. In developing countries including Sub-Saharan Africa, head and neck cancer is rare compared to other cancers. The aims of this study are to estimate the incidence and determine the epidemiological characteristics of head and neck cancer in the population of Niger.

Methods

This is a descriptive retrospective study of head and neck cancer cases, reported to the Niger Cancer Registry in the period 1992-2009. Head and neck cancer includes the following: lip, tongue, mouth (floor, palate and other), salivary glands, tonsils, pharynx (oro-, naso- and hypopharynx), larynx, nose, ear, head and neck not otherwise specified.

Results

In 1992-2009, there were 344 cases diagnosed with head and neck cancer in Niger, which was 4.89% of all cases of cancer reported during this period, with a male-female ratio of 1.49. The incidence rate of head and neck cancer was 2.34 cases per 100 000 persons. Oral cancer was the most common cancer (27.6%), followed by laryngeal and salivary glands cancers (13.1%) and tonsil cancer (10.2%). The mean age at diagnosis of the patients was 42.11±18.24 years. The commonest histological type was squamous cell carcinoma in 27.1% of cases. We registered 11 deaths, with a fatality rate of 3.19%.

Conclusions

Although the incidence rates for head and neck cancers are lower, these cancers include a diverse group of uncommon tumors that frequently are aggressive. Because of the seriousness of cancer in Niger; the health authorities should pay more attention to this pathology through efficient fight strategies.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

284P - Outcomes of metronomic adjuvant chemotherapy with tegafur-uracil in locally advanced head and neck squamous cell carcinoma (ID 297)

Presentation Number
284P
Lecture Time
09:00 - 09:00
Speakers
  • Tsung-jang Yeh (Kaohsiung City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) was the 8th most common cancer worldwide in 2018. Incidence and mortality rates of HNSCC vary by geographical location, and Taiwan has one of the world’s highest incidence rates of oral cancers. Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aims to demonstrate the outcomes of metronomic chemotherapy with tegafur-uracil (UFUR) in locally advanced HNSCC.

Methods

This is a retrospective study. We included 240 patients with locally advanced (stage III or non-distant metastatic stage IV) HNSCC. Operable patients without post-operational high-risk features were excluded. High-risk features were positive surgical margins, extranodal extension (ENE), perineural invasion (PNI) or lymphovascular invasion (LVI). After standard treatment, 96 patients were further treated with metronomic UFUR and 144 patients were not. The last date of follow-up of this study was 5 April 2020.

Results

There were also no statistical differences between both groups in gender, clinical cancer stage and primary treatment choice. However, there were more hypopharynx cancers in UFUR group and more oral cavity cancers in control group. There were significantly more high-grade features, including LVI (P=0.018), ENE (P<0.001), and positive margin (P=0.025) in UFUR group. The median follow-up duration was 31.16 months (range: 3.80-87.38). The overall survival was not reached in the UFUR group and 54.1 months in control group (p =0.008). For disease-free survival (DFS), the median DFS was 54.5 months (95% CI=40.7-not reached) in the UFUR group and 34.4 months (95% CI=25.2-not reached) in the control group (p =0.03). For distant metastasis-free survival, both groups were not reached (p =0.02). In both groups, primary local recurrence was the most common reason of treatment failure. Overall prevalence of adverse event of UFUR was very low and the most common adverse events were low-grade nausea (3.8%), vomiting (3.3%), neutropenia (1.7%) and mucositis (2.1%).

Conclusions

In patients with high-risk and unresectable locally advanced HNSCC, adding UFUR as a metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy was found to significantly improve OS, DFS and DMFS rates with tolerable adverse events.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

285P - Comparison of induction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone in locally advanced nasopharyngeal carcinoma: A meta-analysis (ID 609)

Presentation Number
285P
Lecture Time
09:00 - 09:00
Speakers
  • Xu Guoqiang (Kunming, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and CCRT alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma (NPC). However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced NPC.

Methods

We thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios (HRs) and risk ratios (RRs) using RevMan 5.1.

Results

Seven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that IC plus CCRT improved overall survival (HR=0.74, 95% CI: 0.62-0.88, P< 0.001), progression-free survival (HR=0.66, 95% CI: 0.57-0.77, P< 0.001), distant metastasis-free survival (HR=0.65, 95% CI: 0.43-0.81, P<0.001) and locoregional recurrence-free survival (HR=0.68 95%, CI: 0.54-0.86, P=0.001) versus CCRT alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during CCRT. However, the incidence of leukopenia and mucositis was similar in IC and IC plus CCRT. Furthermore, the subgroup analysis showed better survival outcomes with IC plus CCRT than with CCRT alone in the triweekly cisplatin subgroup (all P<0.01), whereas IC plus CCRT could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR= 0.71, P=0.02; and HR=0.66, P=0.03, respectively).

Conclusions

IC plus CCRT improved survival outcomes in patients with locally advanced NPC versus CCRT. For the weekly cisplatin regimen subgroup, it did not improve remote control or progression-free survival versus CCRT alone, warranting further clarification.

Clinical trial identification

The protocol of our study has been registered with PROSPERO, and the number is CRD42018087074.

Legal entity responsible for the study

The authors.

Funding

People's Government of Yunnan Province (no grant number is applicable).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

286P - Improved diagnostic accuracy on MR imaging in post-surgical recurrent head and neck SCC lesions using decision tree classification system (ID 770)

Presentation Number
286P
Lecture Time
09:00 - 09:00
Speakers
  • Ankush Jajodia (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Recurrent tumors on MRI described as intermediate T2 signal intensity and ADC quantitative values derived from diffusion sequences are prone to discrepancy. In post surgical setting of oral cavity ADC values are prone to artifacts limiting its utility. This investigation aims to build a decision model using quantitative robust parameters derived from MR imaging.

Methods

Four lesion quantitative parameters ( quantitative T2 lesion signal, T2 lesion/muscle signal ratio, T2 lesion /Tongue signal ratio and ADC values) were assessed in 68 lesions (54 malignant,14 benign). Classification analysis was performed using L1 regularization of features in a Logistic regression, Statistical feature selection methods like ANOVA f-value and chi square and lastly a Entropy based feature selection using decision tree. Results include the probability for malignancy for every descriptor combination in the classification tree. Area under the curve (AUC) used as the statistical parameters to find model efficiency was calculated using software "R".

Results

Logistic regression based classifier could predict the probability of cancer based on T2 based features alone. ADC was not found helpful in predicting the disease. Both scores obtained from ANOVA and Chi-square have a different assumptions about distributions of input feature values and output probabilities, but yielded different scores. Both methods point to T2 as most significant in predicting output probabilities of cancer. Lastly, the decision tree showed T2 based features in addition to ADC provide maximum diagnostic value in determining cancer in patients. The area under the curve of the ROC was .940 for additive T2 and ADC and only 0.74 for ADC values alone. The signal ratios (T2 lesion/muscle signal ratio and T2 lesion /Tongue signal ratio) have an AUC 0.96.

Conclusions

Though each method of feature selection has certain shortfalls due to the assumptions but results demonstrate T2 feature outranking all others, indicating its high predictive power in determining the probability of disease. It is therefore possible to train predictive robust models based on T2 quantitative features with high level of accuracy and precision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

287P - Establishment of nasopharyngeal carcinoma organoid culture system and preliminary exploration of drug sensitivity test in vitro (ID 1031)

Presentation Number
287P
Lecture Time
09:00 - 09:00
Speakers
  • Wang X. Wen (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Nasopharyngeal carcinoma (NPC) has a high incidence among malignant tumors in China, accounting for the highest incidence of head and neck tumors. The treatment of recurrent NPC is difficult, and both the traditional in vitro cell line and PDX models have obvious shortcomings. Therefore, it is imperative to establish better disease models, to study further the mechanism of recurrent NPC, and to explore a more effective treatment method. Tumor organoids are tumor micro-organs in which stem cells are cultured in 3D in vitro. They have been verified by histopathology, molecular biology and genomics, and can retain most of the biological characteristics and tumor heterogeneity of primary tumors, which could be the best models for basic and clinical research. This study aimed to culture and identify NPC organoids using NPC biopsy and resected tissues.

Methods

Fifteen fresh nasopharygeal cancer tissue samples (diagnosed by pathology)were collected from NanFang hospital for 3D culture from June 2018 to December 2019. NPC organoids were collected, fixed with 10% formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The expression of CD133/CD44/CD47/BMI-1/EBER were detected by immunohistochemistry and in situ hybridization.

Results

1.Successful establishment of nasopharyngeal carcinoma organoid culture system. A total of 50 NPC samples were collected, and 29 organoids were successfully cultured, with a success rate of 58%. There were 16 primary NPC organoids and 13 recurrent NPC organoids. The success rate of culture of primary and recurrent NPC organoids was 47.06% and 81.25%, respectively. The success rate of culture was mainly related to tissue quality and size, specimen pollution, etc. (P= 0.002). 2. The 3D cultures were identified as NPC organoids. The pathological characteristics of HE staining of 3D NPC cultures were consistent with those of parental tumor tissues, which had typical nuclear atypia. The markers, CD133/CD44/CD47/BMI-1 and EBER, were all positivelv expressed in both 3D cultures and parent tumor tissues.

Conclusions

We have successfully established a NPC organoid model which provides a good reference for future study of the molecular mechanism of NPC.

Legal entity responsible for the study

Li Gang.

Funding

Nanfang Hospital.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

289P - Radiotherapy in advanced nasopharyngeal carcinoma (ID 274)

Presentation Number
289P
Lecture Time
09:00 - 09:00
Speakers
  • Chih Kiang Tan (Kuala Lumpur, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Palliative chemotherapy is the standard of care for patients with advanced nasopharyngeal carcinoma. Radiotherapy may be offered for patients who responded to chemotherapy for local control. However, the dose and fractionation schedules used varies between oncologists.

Methods

An online survey via email was conducted for all practicing oncologists in public hospitals in Malaysia. The questionnaires were sent to 42 oncologists. The questionnaires gathered data on their practice in giving radiotherapy to patients with advanced nasopharyngeal carcinoma who responded to palliative chemotherapy,.

Results

33 oncologists responded to the questionnaire, which gave a response rate of 78.5%. Most oncologists (85%) will give radiotherapy if patients responded to palliative chemotherapy, and 90.9% will give radiotherapy alone without concurrent chemotherapy. The radiotherapy dose fractionation schedules vary among the oncologists, with 55Gy/20 fractions/4 weeks the commonest fractionation used (30.3%), followed by 40Gy/15 fractions/3 weeks (24.2%), and 9.1% choosing schedules such 30Gy/10 fractions/2 weeks, 45Gy/15 fractions/3 weeks, and 70Gy/35 fractions/7 weeks. The other fractionations used are 52Gy/13 fractions/2.5 weeks, 50Gy/25 fractions/5 weeks, 60Gy/25 fractions/5 weeks, 66Gy/33 fractions/6.5 weeks, and 60Gy/30 fractions/6 weeks. Most oncologists will prefer a fractionation schedules of 3-4 weeks duration (75.8%), with high enough dose to give a good local control and avoiding long treatment duration, as the radiotherapy is non-curative in nature.

Conclusions

There are currently no guidelines or consensus on the optimum radiotherapy dose fractionation schedules for this group of patients. The decision for the preferred dose-fractionation schedules have to take into consideration factors such as symptoms, disease extent and comorbidity. An optimum dose-fractionation schedule which does not prolong the treatment duration and giving the best local control is very much needed, especially in situations such as the current COVID-19 pandemic.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO16 - Tuberculous ileitis and hepatic dysfunction in a metastatic nasopharyngeal carcinoma (NPC) patient with complete response following Pembrolizumab (ID 1033)

Presentation Number
YO16
Lecture Time
09:00 - 09:00
Speakers
  • Kin-Sang J. Lau (Hong Kong, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

A 29-year-old lady presented with advanced nasopharyngeal carcinoma (NPC) that metastasized to lymph nodes, bilateral lungs and bones in December 2014. Her disease progressed despite chemotherapy including gemcitabine, platinum, 5-FU, capecitabine, taxane, cyclophosphamide. She received radiotherapy for progressive neck lymph nodes in March 2015 with good response. Her lung metastases further progressed to multiple cannon ball lesions, leading to significantly dyspnea requiring admission and 100% O2. Serum EBV DNA was 120000 copies/mL. Tissue biopsy for PD-L1 TPS was 100%. She was started on IV Pembrolizumab 2mg/kg every three weeks. Her symptoms markedly improved, allowing her to resume work as a life-guard. Her lung lesions resolved on CXR after four cycles, serum EBV DNA fell to 100 copies/mL. FDG PET-CT scan showed complete response after eight cycles.

She was on Pembrolizumab from September 2016 to April 2019 when later she presented to A&E for severe right lower quadrant pain. Computed tomography of abdomen showed terminal ileitis and multiple mesenteric lymph nodes. Colonoscopy was performed, and terminal ileum was biopsied, pathology showed multiple caseating granulomas with langerhan cells, consistent with tuberculous ileitis. Interferon gamma release assay was tested strong positive, indicating past MTB infection. She was started on anti-TB drug with Rifampicin, Ethambutol, Pyrazinamide, Isoniazid. The drug regimen was continued for four months. Pembrolizumab was withheld during that period. Her abdominal pain subsided after antibiotics. The terminal ileitis and mesenteric lymph nodes were resolved on CT scan. Colonoscopy was repeated whic showed no signs of further ileitis.

However, her blood tests showed progressive liver function derangement. Multi-disciplinary management team including microbiologist suggest liver derangement to be anti-TB drug related, with a plan for liver biopsy. Her anti-TB medication was adjusted and liver function gradually normalized. IV Pembrolizumab was re-introduced and continued to two years. FDG PET-CT showed no disease progression, and serum EBV DNA remained below 300 copies/mL.

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e-Poster Display Session (ID 87) Poster Display

Palliative care (ID 1153)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

293P - Prolonged release (PR) oxycodone/naloxone (OXN) for cancer pain (CP) & its impact on bowel function, safety & quality of life (QoL): Systematic review (ID 389)

Presentation Number
293P
Lecture Time
09:00 - 09:00
Speakers
  • Sam Hjelmeland Ahmedzai (Sheffield, S. Yorks, United Kingdom)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

OXN PR, a fixed dose combination of opioid and peripherally-acting mu-opioid antagonist, offers analgesia while reducing opioid-induced constipation (OIC). Few have studied OXN vs other strong opioids for impact on bowel function, safety and QoL in patients with CP.

Methods

Systematic review of literature from PubMed and EMBASE that evaluated analgesia, bowel function, adverse events (AE) and QoL after OXN PR or oral oxycodone (OXY)/morphine/tapentadol PR, or transdermal fentanyl, in adults with moderate-severe CP. Data for outcomes were extracted from publications or clinical study reports.

Results

4 RCTs (OXN vs OXY) were found; no RCT compared OXN vs other strong opioids. Analgesia and safety were comparable with OXN or OXY, except for nausea that was less frequent with OXN (Odds ratio: 0.51 [0.26, 0.97]). Most AEs related to OXN and OXY were mild-moderate severity; most common were gastrointestinal disorders. Improved bowel function (BFI, PAC-SYM) was observed with OXN vs OXY (Table). QoL was comparable with OXN or OXY (Global health status, mean difference: 0.5 [-4.7, 5.7]).

Descriptive findings for bowel function

RCTs Findings OXN vs OXY
BFI
Scores over 4 weeks 2 Δ mean (% improvement) RCT 1: -25.1 (39.2%) vs -13.6 (21.7%) RCT 2: -36.0 (50.7%) vs -25.0 (36.8%)
Score comparison at week 4 1 LS mean difference (SE) -11.1 (4.00)
95% CI [-19.0, -3.2]
P value 0.006
PAC-SYM
Total score 1 Δ mean (% improvement) -7.0 (40.3%) vs -2.7 (15.1%)
P-value§ 0.0014
Symptom frequency 1 Δ mean (% improvement) -1.1 (41.9%) vs -0.3 (12.9%)
P value§ <0.001

baseline to week 4 adjusted for baseline using ANCOVA model. §between-group difference; derived from summary statistics LS, least squared.

Conclusions

Systematic review found only direct comparisons of OXN vs OXY in RCTs of CP. OXN provided similar analgesia and safety to OXY for CP with less nausea and improved bowel function, in terms of constipation symptoms. OXN is a valuable analgesic option in patients with OIC or nausea from cancer itself or anticancer treatment. Although limited, this meta-analysis confirms existing evidence on OXN’s efficacy and tolerability in patients with moderate-severe CP and highlights that few data on OXN in CP is available.

Editorial acknowledgement

Editorial assistance was provided by Wei Yi Kwok and Geraldine Toh from Tech Observer Asia Pacific Pte Ltd.

Legal entity responsible for the study

Mundipharma Singapore Holding Pte Ltd.

Funding

Mundipharma Singapore Holding Pte Ltd.

Disclosure

S.H. Ahmedzai: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Mundipharma. L. Langenhoven: Advisory/Consultancy, Speaker Bureau/Expert testimony: Mundipharma. C. Minnaert, Y. Hadjiat: Full/Part-time employment: Mundipharma. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

294P - Interventional pain treatment in patients with pain syndrome in advanced tumours of small pelvis (ID 982)

Presentation Number
294P
Lecture Time
09:00 - 09:00
Speakers
  • Yakhyo Ziyaev (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

More than a third of small pelvis cancer cases in Uzbekistan are diagnosed in the late stages, where the main goal of medical interventions is to increase life expectancy with maximum maintenance of the quality of life. Opioid prescription and opiophobia in medical personnel make it harder to control pain in this group of patients, decreasing the quality of their life.

Methods

34 patients with locally advanced tumors of small pelvis (17 rectal cancer, 11 cervical cancer, 6 prostate cancer) with pain syndrome by visual analog scale (VAS) 8-10 were selected as the study group. Patients were treated in National cancer center of Uzbekistan in 2017-2020. Epidural catheter was placed in V4-5. Solution of bupivacaine 2.5% 20 ml with 1% of morphine injected at primary point. Then, 5 ml of bupivacaine 2.5% every 6 hours, 1 ml of 1% morphine every 12 hrs. Mean period of catheter placement was 23,6 days (7-36). in order to decrease the possibility of infection wide spectrum of antibiotics and wound dressing were administered. Control group included 34 patients with locally advanced tumors of small pelvis (20 rectal cancer, 12 cervical cancer, 2 prostate cancer) with pain syndrome by visual analog scale (VAS) 8-10. They underwent standard WHO pain ladder therapy morphine 1%-1 ml every 4-6 hrs ± ketorolac 30 mg – 1 ml.

Results

Withing the 20 minutes of administering, median pain syndrome by VAS was 0.78 (0-4). 6 (17.6%) patients admitted headache, 3 dizziness (8.8%). 2 patients admitted 1st grade nausea (5.9%). Constipation was not admitted in the main group. Drowsiness was admitted in 7 patients (20.6%). All of the symptoms disappeared within the 7 days period of hospitalization. In control group, the mean pain syndrome was 4.6 (0-7) by VAS. Drowsiness effect was observed in 27 patients (79.4), however, 21 (61.8%) cases this effect regressed in 7-day period. In 3-months observation period, 11 (32.6) patients from second group had complains on constipation which was resolved with laxatives and enemas.

Conclusions

Analgesia with usage of long-term epidural catheter placement allowed to achieve better pain control, lower opioid usage and avoid severe complications in patients with severe chronic pain syndrome of small pelvis tumors.

Clinical trial identification

N/A

Legal entity responsible for the study

National Cancer Center of Uzbekistan.

Funding

National Cancer Center of Uzbekistan.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

295P - Assessment of the impact of palliative care on the quality of life in advanced non-small cell lung cancer patients (ID 179)

Presentation Number
295P
Lecture Time
09:00 - 09:00
Speakers
  • Sabin S. Katpattil (Mangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

During the last two decades, health-related quality of life (QoL) measurements have been an important issue in understanding the difficulties perceived in many diseases. It is important to assess the health-related quality of life to know the extent of diseases and conditions affecting individual’s general well-being. Studies have shown the effect various determinants of Quality of Life (QoL) in lung cancer patients. This study was done to assess the QoL in individuals with non- small cell lung cancer undergoing palliative care.

Methods

Materials and Method: Data on QoL were collected using a modified MOS-SF form-32. The study was done in 27 individuals before and after providing supportive or palliative care. A random mixed linear model was used to assess impact of palliative care on Quality of Life with Physical Health Summary score and Mental Health Summary score as main outcomes. All the possible confounding factors were controlled in the study.

Results

When values were compared before and after giving palliative care the Physical Health Summary score decreased considerably. (diff=-2.12; 95% CI: [-4.08, -0.63]) with small to medium effect sizes. The PHS Score remained lower after being on palliative care for more than 2 years (diff=-5.86; 95% CI: [-7.89, -3.63]).]). The Mental Health summary score didn’t change significantly after giving palliative care (diff=-5.86; 95% CI: [-7.89, -3.63]). The Mental Health summary score was higher after HAART for more than 5 years when compared prior to infection.

Conclusions

Quality of life is an important determinant in the course of lung cancer. Palliative or supportive care can play a vital role in improving the quality of life in patients with lung cancer.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

296P - Outcomes of repeat transhepatic percutaneous biliary drainage in patients presenting with recurrent malignant biliary stricture (ID 578)

Presentation Number
296P
Lecture Time
09:00 - 09:00
Speakers
  • Deevia Hanji (Coventry, United Kingdom)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Unresectable malignant biliary obstruction confers a poor prognosis. Drainage of the biliary system with percutaneous trans-hepatic biliary drainage (PTBD) is offered with the intent of palliation of symptoms or to enable SACT (systemic anti-cancer treatment) but is associated with significant morbidity and mortality. Repeat PTBD for oncology patients was reviewed, asessing factors associated with poor outcomes to improve patient selection for PTBD.

Methods

Retrospective study of patients undergoing repeat PTBD at University Hospital Coventry & Warwickshire between 2015-2020. By collating data from the hospital database, morbidity and mortality of a repeat PTBD was reviewed, and factors associated with increased mortality noted.

Results

27 cases of repeat PTBD for recurrent malignant biliary obstruction were identified and analysed out of a total of 211 PTBD procedures performed for malignant biliary obstruction. Median survival was 81 days (range 22-455), median length of stay 15 days (range 2-52), and median age 66 (range 34-81). Mortality: in hospital was 3.7%, 7 day 0%, 30 day 7.4% and 90 day 48%. Factors associated with lower median survival rates were: male gender, age > 65, receiving SACT (either before or after PTBD), complications of post procedure sepsis and a pre-procedure bilirubin of greater than 100 umols/L. Patients receiving SACT within 3 months prior to PTBD had better median survival compared to those who had SACT > 3 months prior (90 days vs 72). SACT following PTBD had the highest median survival (278 days). Comparatively, cases receiving no chemotherapy (pre or post PTBD) had the lowest median survival (69 days)

Median survival following PTBD (days)

Female Male
110 68
Age <65 Age 65+
96 81
SACT No SACT
91 69
No sepsis Sepsis
103 75
Bilirubin <100umol/L Bilirubin >100umol/L
96 83
.

Post procedure sepsis reduced median survival and increased median length of stay from 10 to 17 days.

Conclusions

Repeat PTBD in this cohort of patients showed a similar median survival to those undergoing first episode of PTBD (81 vs 88 days respectively). Features associated with better outcomes that could potentially guide patient selection include: lower age, female gender, lower bilirubin pre-procedure and being on active SACT or progressing to SACT post procedure.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

297P - Factors affecting duration of admission in the palliative medicine ward of a tertiary cancer hospital: A pilot, investigator initiated, review of services (ID 225)

Presentation Number
297P
Lecture Time
09:00 - 09:00
Speakers
  • Rahul D. Arora (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Palliative care services are bieng provided to advanced cancer patients, and have traditionally included symptom directed therapy, counselling regarding goals of care and discussions centered around aggressiveness of care. An early palliative mliaison is bieng offered to patients with recently diagnosed tumours, but the ambit, purview and scope of these services has remained essentially unchanged.

Methods

Details of 127 patients admitted to the ward between over the course of three months were recorded and analysed.

Results

Analgesic titration (54 percent), interventional pain management (15 percent) and provision of supportive care services (23 percent) were the most common indications for admission. 44/123 patients (35.7 percent) received services which can be considered to be within the purview of supportive care. Bisphosphonate infusion for prevention of skeletal related events (12), pigtail catheter insertion for malignant pleural effusion (4), ultrasound guided therapeutic paracentesis (5), octreotide infusion for symptom control in neuroendocrine tumours and malignant bowel obstruction (3), management of difficult to control symptoms including dyspnoea and pain, malignant bowel obstruction (2), chemotherapy related complications (including febrile neutropenia, mucositis and diarrhea) were among services provided upon inpatient admission. 3 patients recieved chemotherapy. 13/127 recieved consultation liasion during their stay in the ward. Medical oncology liaison was the most commonly sought. The most commonly prescribed opioid was morphine followed by fentanyl and tramadol. Average duration of stay was 1.2 days with the longest admission lasting 5 days. The duration of stay was significantly longer for those who also recieved supportive care (p<0.01). Morphine equivalent daily dose, number of medications prescribed and Eastern cooperative oncology group performance status did not have any effect on the duration of stay.

Conclusions

The nature of services provided under the purview of this model, has the potential to ignite a larger debate on the impending and urgent need to redefine the scope of conventional Palliation.

Legal entity responsible for the study

Rahul D. Arora.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Precision medicine (ID 1154)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

304P - Identification of nine lncRNAs signature for predicting survival benefit of melanoma patients treated with immune checkpoint inhibitors (ID 395)

Presentation Number
304P
Lecture Time
09:00 - 09:00
Speakers
  • Jian-Guo Zhou (Zunyi, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immune checkpoint inhibitors (ICI) have been widely used in melanoma, but to identify melanoma patients with survival benefit from ICI is still a challenge. There is an urgent need for prognostic signatures improving the prediction of immunotherapy responses of cancer patients.

Methods

We used data from EMBL-EBI database and analyzed RNA-seq information and clinical profiles in melanoma. Weighted gene co-expression network analysis (WGCNA) was used to identified the key module, then nonnegative matrix factorization (NMF) was conducted to cluster patients into two different cluster and compared them regarding overall survival (OS) and progression-free survival (PFS). Subsequently, the differentially expressed genes (DEGs) between different clusters were identified and their function and pathway annotation were performed.

Results

91 melanoma biopsies with complete survival information were included in our analyses and we first identified the key module (magenta) by WGCNA, then identified nine prognostic lncRNAs (ENSG00000258869, ENSG00000179840, ENSG00000206344, ENSG00000226777, ENSG00000205018, ENSG00000204261, ENSG00000163597, ENSG00000197536, and ENSG00000263069) signature that predicted for OS and PFS in patients treated with ICI by NMF. Finally, enrichment analysis showed that the functions of DEGs between two consensus clusters were mainly related to the immune process and treatment.

Conclusions

the nine lncRNAs signature is a novel effective predictor for OS and PFS in melanoma patients treated with ICI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

305P - Novel co-occurring genomic alterations associated with prediction and prognosis in lung adenocarcinoma (ID 803)

Presentation Number
305P
Lecture Time
09:00 - 09:00
Speakers
  • Xin Zhao (Shenzhen, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Actionable mutation detection by targeted multiple gene panel sequencing is increasingly becoming a routine test in the clinical treatment of non-small cell lung cancer. Although it helps patients choose their own personalized drugs, most mainly focused on single actionable event and ignored the other driver variation which could affect the efficacy of the targetable drugs and patients’ outcome.

Methods

Fresh frozen tumors, pleural effusion or FFPE tumors with matched peripheral blood were collected from 235 patients with lung adenocarcinoma (LUAD) before therapy. All of the samples were sequenced using commercial gene panel OseqTM series. The genetic molecular profiles, correlations between genetic variations and patient's prognosis were analyzed.

Results

A total of 1713 somatic variations were detected in our cohort including single-nucleotide variants, insertion/deletions, copy number alterations and structural variations. Over 50% of patients carried either EGFR or TP53 alteration. The tumor variant allele frequency of TP53 was a prognostic indicator for LUAD patient. The co-occurring genomic alterations were associated with patients' outcome, especially for genes co-mutated with EGFR, ERBB2 and KDR in the EGFR tyrosine kinase inhibitor resistance pathway. In addition, MYC amplification alone was insufficient as an independent prognostic predictor for LUAD. Moreover, the DNA damage repair genes including ATM, BRCA1and BRCA2 were more likely to alter in patients with wild-type TP53 (TP53wt). The alterations on STK11 and KRAS were enriched in TP53wt and DDRmut individuals and slightly corelated with prognosis of LUAD patients.

Conclusions

We presented an integrated analysis of genetic and clinical outcome features in LUAD cohort. Several novel pairs of concurrent gene variation were found which associated with patients' survival and could be prognostic predictors for treatment evaluation. Our work also shed further light on the genomic subtyping based on DDR genes as promising prognostic biomarkers in LUAD and provide a larger picture of multiple gene sequencing for helping to find optimal treatment in precision anticancer therapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

306P - Detection of anaplastic lymphoma kinase (ALK) mutations using circulating tumour DNA (ctDNA) in advanced non-squamous non-small cell lung cancer (non-Sq-NSCLC) in Asia (ID 947)

Presentation Number
306P
Lecture Time
09:00 - 09:00
Speakers
  • Kirsty W. Lee (Hong Kong, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

ALK gene rearrangement occurs in 3-7% of non-Sq-NSCLC. Tumor ALK testing by immunohistochemistry (IHC) is recommended. Next generation sequencing (NGS) and fluorescent-in-situ hybridization are validated for samples with inconclusive IHC staining. NGS testing of plasma ctDNA is non-invasive, allowing diagnosis where tissue is inaccessible, and detection of resistance mutations post-progression. One study has reported clinical utility of ALK testing using NGS on plasma, but data are otherwise limited to small samples. We assessed clinical utility of ctDNA NGS for ALK testing for non-Sq-NSCLC in Asia.

Methods

Between September 2015 to May 2020, 464 plasma specimens from 413 patients were analyzed. ctDNA was genotyped using Guardant360 (Guardant Health, Redwood City CA USA). Data on clinicopathologic features and treatment status were extracted from database (Sanomics Ltd, Hong Kong).

Results

ALK fusion and/or resistance mutations were detected in ctDNA of 24 (6%) non-Sq-NSCLC patients. 12 patients (50%) were male. 19 (79%) were adenocarcinoma, 5 (21%) were unknown. Tumor ALK status was available in 21 patients: 13 were ALK positive, 8 previously tested negative. ALK fusion partners included EML4 (85.7%), STRN (9.5%), and KIF5B (4.8%). ALK resistance mutations were detected only in patients with prior ALK inhibitor treatment (8/12, 67%). 13 types of resistance mutations were identified: G1202R, then L1196M, were the most frequent. (Table)

Patient no. 1a 1b 2a 2b 3a 3b 3c 4a 4b 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Prior TKI treatment NA Y NA NA Y Y Y O O NA O Y Y Y N Y N Y Y Y O Y NA Y O Y NA O O
ALK TKI Crizotinib Y Y Y Y Y NA
Ceritinib Y Y Y
Alectinib Y Y Y Y Y Y Y Y Y Y
Lorlatinib Y Y Y
ALK fusion EML4-ALK P P P P P P P P P P P P P P P P P P P
KIF5B-ALK P
STRN-ALK P P
ALK resistance mutation E1210K P
D1203N P
F1174C P
F1174L P P P
G1202R P P P P P
G1269A P
I1171N P
I1171T P P
L1152R P
L1196M P P P P
L1196Q P
L1198F P P
V1180L P P

NOTE: TKI - tyrosine kinase inhibitor; a, b, c - 1st, 2nd, 3rd ctDNA NGS test; NA - not available; Y - yes; N - no; O - other therapy; P - positive.

Conclusions

NGS testing for ALK fusions and genomic alterations in plasma ctDNA has clinical utility in non-Sq-NSCLC patients in guiding ALK targeted treatment at initial diagnosis and upon cancer progression. Detection rate and distribution of ALK fusion partners are comparable to existing data of tumor ALK testing. Further data on ALK treatment outcomes of patients with detectable ALK fusion on plasma ctDNA is warranted.

Legal entity responsible for the study

Sanomics Limited.

Funding

Has not received any funding.

Disclosure

K.W.C. Lee, S.T. Wu, P.Y. Lo, C.T. Choy, T.C. Kwong, Y.T.N. Lau. L. Lin, S.W. Lau: Full/Part-time employment: Sanomics Limited.

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e-Poster Display Session (ID 87) Poster Display

307P - Development of circulating free DNA methylation markers for thyroid nodule diagnostics (ID 1016)

Presentation Number
307P
Lecture Time
09:00 - 09:00
Speakers
  • Shuibing Hong (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The incident rate of thyroid nodules has risen globally, thus it is critical to identify malignancy among benign lesions. Currently available molecular diagnostics for malignant nodules have not achieved the desired degree of accuracy. We aimed to identify DNA methylation markers to accurately classify benign and malignant nodules, and to develop tools for non-invasive screening of thyroid cancer.

Methods

Marker screening was performed on papillary thyroid cancer (PTC, 37 tissues, 55 plasmas), benign nodules (BTN, 37 tissues, 55 plasmas) and normal samples (20 buffy coats; 123 plasmas) by MONOD+ assay. We identified differential markers by Wilcox rank sum test using Benjamini-Hochberg procedure to control false discovery rate. Predication models were built using machine-learning algorithms including random forest and support vector machine. They were validated using public DNA methylation data of thyroid tissues. Candidate markers were developed into a targeted sequencing panel and were validated on plasma DNA samples (115 PTC, 102 BTN). Best-performing markers were developed into an improved panel to classify additional plasma DNA samples of malignant or benign thyroid nodules.

Results

From the MONOD+ data we identified over 1000 DNA methylation markers significantly differential between malignant and benign nodules. We built a classification model by random forest method, which classified DNA methylation profiles of thyroid nodules at a sensitivity of 90.5% and a specificity of 91.9% (95% CI, 0.91-1.0). We produced a targeted sequencing panel using those markers and sequenced plasma DNA of PTC and benign nodules. Two thirds of them were used as a training cohort to build a prediction model, which classified the remaining samples at an accuracy of 72%. We selected the best-performing markers to build an advanced version of panel, which classified additional over 500 plasma DNA samples of thyroid nodules with increased sequencing depth to improve the accuracy and consistency in classification.

Conclusions

Our study demonstrates that DNA methylation markers can robustly differentiate thyroid nodules based on their malignancy. They are thus promising candidates to develop non-invasive diagnostics for thyroid cancer screening.

Legal entity responsible for the study

The First Affiliated Hospital, Sun Yat-sen University.

Funding

The First Affiliated Hospital, Sun Yat-sen University.

Disclosure

Z. Su, Q. He: Shareholder/Stockholder/Stock options, Full/Part-time employment: Singlera Genomics. L. Cheng: Full/Part-time employment: Singlera Genomics. R. Liu: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Singlera Genomics. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

308P - The genomic landscape of non-small cell lung cancer (NSCLC) in East Asia using circulating tumour DNA (ctDNA) in clinical practice (ID 679)

Presentation Number
308P
Lecture Time
09:00 - 09:00
Speakers
  • Byoung C. Cho (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

We investigated the landscape of clinically relevant mutations in ctDNA from NSCLC patients in East Asia tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360) as part of clinical practice. This assay identifies single nucleotide variants (SNV), insertions (ins) and deletions (del), fusions, and amplifications (amp), with complete exon sequencing of multiple genes including EGFR, ERBB2, and KRAS.

Methods

Test results from Hong Kong, Korea, Taiwan, Japan and Southeast Asia were reviewed (cut-off June 2020). We identified cases with a diagnosis of “lung cancer,” excluding neuroendocrine, sarcomatoid, and pure squamous histology. Samples from patients enrolled in prospective clinical trials were excluded. Clinically relevant biomarkers were mutations in EGFR, ERBB2, or KRAS; BRAF V600E; MET amp or exon 14 skipping; and ALK, ROS1, RET, or NTRK1 fusions. Synonymous mutations and variants of unknown significance were not considered.

Results

Plasma from 1219 advanced non-squamous NSCLC patients was tested. Samples came from 663 women and 556 men, median age 62 years. Median turnaround time was 7 days from sample receipt to report. ctDNA was identified in 1034 samples (85% detection rate), with median variant allele fraction 0.6%. There were 718 samples (69%) with alterations in at least one clinically relevant biomarker: EGFR (49%), KRAS (8%), ERBB2 (4%), ALK (3%), RET (2%), MET (2%), BRAF (1%), and ROS1 (<1%). Co-mutations were detected in <1%. Potentially actionable EGFR alterations other than L858R or exon 19 del were found in 106 samples (13%), including exon 19 ins (1); exon 20 ins (25); and activating SNV (80) such as L718X (14), L861Q (7), G719A (7), and E709A (5). KRAS G12C was present in 22 samples (2%).

Conclusions

In the clinical practice setting, comprehensive NGS detected relevant biomarkers in 69% of plasma samples with ctDNA from patients with advanced non-squamous NSCLC. Using a single assay, both common and rare driver mutations could be found in a timely manner, obviating the need for multiple tests to identify less common actionable alterations.

Legal entity responsible for the study

Guardant Health AMEA.

Funding

Has not received any funding.

Disclosure

B.C. Cho: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MOGAM Institute; Honoraria (self), Research grant/Funding (institution): Dong-A ST; Honoraria (self), Research grant/Funding (institution), Licensing/Royalties: Champions Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Yuhan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Medpacto; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer; Honoraria (self): Guardant Health AMEA; Advisory/Consultancy: Takeda; Research grant/Funding (institution): AbbVie. H.H.F. Loong: Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli-Lilly; Advisory/Consultancy: Illumina; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Guardant Health; Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Mundipharma. H.R. Kim: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Roche. M. Lee: Full/Part-time employment: Guardant Health AMEA. S. Olsen: Full/Part-time employment: Guardant Health AMEA; Shareholder/Stockholder/Stock options: Guardant Health, Inc.; Shareholder/Stockholder/Stock options: AstraZeneca. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

309P - Improved diagnostic accuracy in MRI breast lesions using a classification system and multilayer perceptron neural network (ID 909)

Presentation Number
309P
Lecture Time
09:00 - 09:00
Speakers
  • Venkata Pradeep Babu Koyyala (New Delhi, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The American College of radiology proposed BI-RADS lexicon lacks defined rules which direct conversion of specific imaging features into a diagnostic category, results in a discrepancy of reporting. This study compares results from multilayer Perceptron neural network and a classification tree.

Methods

A total of 316 lesions with successive histological verification (221 malignant, 95 benign) were investigated. Six lesion criteria's were assessed by 2 readers in consensus. Classification analysis was performed using the chi-squared automatic interaction detection (CHAID) method. Results include the probability for malignancy for every descriptor combination in the classification tree. Simultaneously a multilayer Perceptron neural network was developed by using SPSS software.

Results

A classification tree incorporating 6 lesion descriptors with a depth of 4 ramifications (1- ADC values; 2 -root sign; 3- enhancement pattern; 4 - oedema) was calculated. Of all 316 lesions, 38 (40 %) and 212 (95.9 %) could be classified as benign and malignant with an accuracy above 95 %, respectively. Overall diagnostic accuracy was 79.1 %. The multilayer perceptron network segregated the lesions into training and testing sets in a ratio of 7:3. With a hyperbolic tangent activation function, there were six units of hidden layer and the model show a 20% and 17% incorrect predictions in the training in the testing sets. The diagnostic accuracy of malignant and benign lesions was 92% and 52 % in both the training and testing sets. The area under the curve of the ROC was .855. The order of importance of synaptic weights calculated from the model were ADC ( 0.257), Internal enhancement (0.233), ROOT SIGN (0.175), Margins (0.138), Curve type (0.138), edema (0.038) and mass / non mass (0.021).

Conclusions

The classification algorithm correctly classified 95 % malignant lesions with accuracy above 95 %. The neural network model showed good results on internal validation and revealed ADC to be the most significant parameter with the least importance to morphological classification into mass and non-mass lesions. Also, the dynamic contrast curve patterns were more significant than margins.

Legal entity responsible for the study

Rajiv Gandhi Cancer Institute and Research Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

310P - Genomic biomarker detection in East Asian clinical practice using circulating tumour DNA (ctDNA) from patients with gastrointestinal (GI) tract cancers (ID 667)

Presentation Number
310P
Lecture Time
09:00 - 09:00
Speakers
  • Sadakatsu Ikeda (Tokyo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Detection of genomic biomarkers in ctDNA may guide treatment decisions for patients with advanced stage GI tract cancers. We summarized the frequency of common and clinically relevant alterations from East Asian patients with common GI cancers whose blood was tested by a commercially available comprehensive next generation sequencing (NGS) assay (Guardant360).

Methods

Anonymized test results from Japan, Korea, Taiwan, Hong Kong, and Southeast Asia were reviewed (cut-off June 2020). We identified cases with a diagnosis of colorectal adenocarcinoma (CRC), pancreatic adenocarcinoma (PC), gastric and gastroesophageal adenocarcinoma (GEC), and biliary tract carcinoma (BTC). Samples from patients enrolled in prospective clinical trials were not included. Synonymous mutations and variants of unknown significance were excluded.

Results

Among 191 plasma samples from CRC patients, ctDNA was detected in 174 (91%). Alterations included TP53 (79%), APC (61%), KRAS (47%), PIK3CA (18%), FGFR1 amp (11%), NRAS (6%), BRAF V600E (6%), ERBB2 amp (5%), MET amp (5%), FGFR2 amp (4%). In 236 samples from PC patients (204 with ctDNA, 86%), alterations included: TP53 (70%), KRAS (69%), PIK3CA (4%), BRCA2 (3%), FGFR1 amp (3%), BRCA1 (1%). In 74 samples from GEC cases (63 with ctDNA, 85%), alterations included: TP53 (59%), ERBB2 amp (16%), KRAS (11%), PIK3CA (6%), FGFR2 amp (6%), MET amp (5%), FGFR1 amp (3%). In 97 samples from BTC patients (84 with ctDNA, 87%), alterations included: TP53 (60%), KRAS (17%), PIK3CA (13%), IDH1 (10%), ERBB2 (4%), FGFR1 amp (4%), IDH2 (1%), BRCA2 (1%), FGFR2 amp or fusion (1% each).

Conclusions

NGS of ctDNA from clinical samples identified common and clinically relevant genomic alterations in East Asian patients with advanced GI cancers. The type and frequency of alterations for each tumor type were similar to those previously reported from tumor tissue banks, although there may be enrichment for resistance mutations due to prior treatment. Given the ease of blood collection over repeat tissue biopsy, these data support consideration of ctDNA NGS for guiding treatment decisions in patients with advanced GI cancers.

Legal entity responsible for the study

Guardant Health AMEA, Inc.

Funding

Guardant Health AMEA, Inc.

Disclosure

M. Muto: Research grant/Funding (institution): Chugai Pharma; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mitsui Knowledge Industry; Research grant/Funding (institution): Sysmex; Research grant/Funding (institution): Riken Genesis; Research grant/Funding (institution): KBBM Kyoto Bridge for Breakthrough Medicine. M. Lee: Full/Part-time employment: Guardant Health AMEA, Inc. S. Olsen: Shareholder/Stockholder/Stock options: AstraZeneca; Shareholder/Stockholder/Stock options: Guardant Health, Inc.; Full/Part-time employment: Guardant Health AMEA, Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

311P - Effect of chemotherapy on fatty liver occurrence in breast and gastrointestinal cancer patients (ID 157)

Presentation Number
311P
Lecture Time
09:00 - 09:00
Speakers
  • Seyed Alireza Javadinia (Mashhad, Iran)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy is one of the fundamental treatments in cancer patients, which has significantly improved survival rate. Alongside positive effects, many side effects. One of major side effects of these drugs is hepatotoxicity, initially develops as fatty liver and hepatic steatosis, but progresses to liver failure if harmful factor persist. To determine prevalence of fatty liver in breast and gastrointestinal cancers during and after chemotherapy and to investigate some of its effective causes.

Methods

This longitudinal cohort study was performed breast or gastrointestinal cancer patients undergoing chemotherapy at the Oncology Clinic of Birjand University of Medical Sciences, 2016-2017. Before and after chemotherapy, the patients were evaluated by sonography for fatty liver. Data were imported into SPSS software version 19 and analyzed by Chi-Square (or Fisher Test) and McNemar at 5% significance level.

Results

A total of 152 patients were enrolled in the study, of whom 85 had breast cancer and 67 had gastrointestinal cancers. Most patients were in age group of 45-54 years old (48 cases, 31.6%). Mean body mass index (BMI) was 23.17 ± 4.52. Frequency of fatty liver before and after chemotherapy increased from 2% to 46.7% in all patients (p = 0.0001). Frequency of fatty liver after chemotherapy was significantly higher in females than males (34.7 and 52.4%, respectively, p=0.04). There was no significant relationship between chemotherapy induced fatty liver with age (p=0.9), BMI (p=0.17), history of diabetes mellitus (p=0.2), and metabolic syndrome presence (p=0.4). The highest frequency of fatty liver was observed in patients treated with AC-T, FOLFOX and ECF with 53.5%, 42.9% and 29.2%, respectively (p = 0.09).

Conclusions

Results showed that chemotherapy is associated with a significantly increased risk of fatty liver occurrence, which is higher in women than men. However, occurrence of fatty liver following chemotherapy, regardless of diabetes, metabolic syndrome or BMI, as well as age of the patients, can be expected in all scenarios.

Legal entity responsible for the study

Dr. Payam Izadpanahi from Reza Radiotherapy Oncology Center (RROC).

Funding

Birjand University of Medical Sciences.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

312P - Identification of neoantigen-specific T cell response and anti-tumour immunity in pancreatic cancer (ID 171)

Presentation Number
312P
Lecture Time
09:00 - 09:00
Speakers
  • Xiaoxiao Du (Hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pancreatic cancer is a highly aggressive malignancy with relatively low morbidity, which is marked by insidious clinical symptoms but rapid development. The therapeutic options of PC are limited for the insensitivity of traditional chemoradiotherapies. The neoantigen-based vaccine is an emerging tumor immune therapeutic option, but limited evidence proved the efficient therapeutic response in pancreatic cancer.

Methods

Whole exome sequencing and bioinformatic analysis as well as quantitative real-time PCR of our previously established human pancreatic cancer cell line were performed to identify neoantigen candidates. The Immunogenicity of prioritized neoantigens was evaluated by analyzing the INF-γ secretion of neoantigen-induced T cell. The antitumor immunity of neoantigen-specific Cytotoxic T cells was examined by the cytotoxicity assay.

Results

The commutative analysis and quantitative real-time PCR identified 13 candidate neoantigens of our previously established human pancreatic cancer cell line PDXPC1 which was confirm as a multi-drug resistant cancer cell line. 4 of 13 candidate neoantigens can be recognized by the immune system and induced strong neoantigen-specific T cell response. The cytotoxic activities mediated by neoantigen-specific T cells significantly inhibited the growth of PDXPC1 tumor cells. Noteworthily, T cells recognized 3 of 4 neoepitopes via the presentation of dendritic cells.

Conclusions

In conclusion, the neoantigens selected by the next generation sequencing and computational algorithm can target the tumor inhibition of pancreatic cancer, which represent a new powerful approach for multidrug resistance and suggest a general strategy for personalized cancer immunotherapy in pancreatic cancer.

Legal entity responsible for the study

The authors.

Funding

The Natural Science Foundation of Zhejiang Province.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

313P - Diagnostic value of micro RNA (miRNA) in renal cell cancer: A meta-analysis and systemic review (ID 583)

Presentation Number
313P
Lecture Time
09:00 - 09:00
Speakers
  • Jestoni V. Aranilla (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Quantitative analyses of miRNA are potential methods for the detection of carcinoma. Some studies have revealed the importance of microRNAs (miRNAs) function as biomarkers in diagnosing renal cell carcinoma. However, some results are discordant. This study is the first to systematically evaluate the accuracy of circulating miRNA for the diagnosis of renal cell carcinoma found in plasma, serum and urine by conducting meta-analysis.

Methods

We searched PubMed, Embase, Cochrane Library and Google Scholar databases systematically for relevant literatures up to January 10, 2020. The HSROC model was used to calculate the pooled diagnostic parameters and summary receiver operator characteristic (SROC) curve in this meta-analysis, thereby estimating the whole predictive performance. Meta-regression was performed to identify the sources of heterogeneity. All analyses were conducted using RevMan 5.3, MetaDTA, Metadisc Ver 3.0 and Medcalc Ver 19.

Results

This meta-analysis included a total of 18 studies in 12 researches, including 817 renal cell carcinoma patients and 622 healthy controls. The summary estimates for quantitative analysis of miRNA in renal cell carcinoma were as follows: sensitivity, 0.80 (95% confidence interval (CI), 0.75– 0.83); specificity, 0.69 (95% CI, 0.61–0.76); positive likelihood ratio, 2.6 (95% CI, 2.0– 3.2); negative likelihood ratio, 0.28 (95% CI, 0.22–0.34); diagnostic odds ratio, 9.2 (95% CI, 5.7–12.8); and area under the curve, 0.74 (95% CI, 0.70–0.78). Additionally, sub-group and meta-regression analyses revealed that there were no significant differences between ethnicity, year of publication, sample type and miRNA profiling. There was no statistical significance for the evaluation of publication bias.

Conclusions

Current evidence suggests that quantitative analysis of miRNA has acceptable sensitivity but unsatisfactory specificity for the diagnosis of renal cell carcinoma. Further large-scale prospective studies are required to validate the potential applicability of using miRNA alone or in combination with diagnostic test for renal cell carcinoma and explore potential factors that may influence the accuracy of renal cell carcinoma diagnosis.

Legal entity responsible for the study

Jestoni V. Aranilla MD.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

314P - Comprehensive microbial signatures and genomic profiling in tumour samples using next generation sequencing (ID 801)

Presentation Number
314P
Lecture Time
09:00 - 09:00
Speakers
  • Mei Qi Yee (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Infectious agents account for 13-20% of new cancer cases worldwide and may have a role in the origin and progression of cancers and pathogenesis. Unfortunately, most commercially available genomic NGS assays neglect this increasingly important information. Herein, we describe next-generation sequencing (NGS) assays, OncoKey SL60 Plus and SL 525 Plus, that identifies DNA and RNA variants, as well as microbial signatures in various tumor types.

Methods

The automated hybridization capture-based NGS tests, OncoKey SL60 Plus and SL525 Plus, target 60 and 525, respectively, clinically relevant genes for small variants, MSI, splice variants, CNV and fusions, including 6 oncogenic viruses: EBV, HCV, HBV, MCPyV, KSHV and 30 subtypes of HPV, and 4 oncogenic bacteria: H. pylori, S. Typhi, S. gallolyticus and C. pneumoniae. Various commercial FFPE reference materials, cell lines harboring oncogenic viruses, and 32 FFPE clinical samples were characterized with the assays and sequenced on both the Illumina® MiSeq and NextSeq Systems.

Results

All expected DNA variants and RNA fusions in reference standards from as little as 40 ng of DNA/RNA input. In clinical samples, NGS results generally concurred with previous FISH/IHC and other molecular characterization thus demonstrating and equivalent accuracy. MCPyV and HBV were detected in MKL-1 and PLC/PRF/5 cell lines respectively, both of which are known carriers. Of the 32 FFPE samples, HPV16 and EBV were identified in 2 head and neck samples thus suggesting possible etiological roles. The presence of HPV and EBV was subsequently confirmed with IHC. In the EBV positive sample, BRCA2 p.G602fs mutation was also detected thus suggesting the patient may be a suitable candidate for PARP inhibitor therapies. In the HPV16 positive sample, PIK3CA p.R88Q was detected thus suggesting the patient may benefit from enroling into PIK3CA inhibitor trials.

Conclusions

Identifying virus and bacteria as etiological agents aids our understanding of the microbiome and cancer, diagnosis and treatment. NGS tools, such as the OncoKey SL60/525 Plus, provide rapid, high throughput and cost-effective strategies for comprehensive microbial and genomic profiling.

Legal entity responsible for the study

Vela Research Singapore.

Funding

Vela Research Singapore.

Disclosure

M.Q. Yee, Y.L. Kok, P. Ariyaratne, Y. Yu, O. Scully, D. Tay, C. Tang, T. Ong, H. Suhardi, K.K.M. Aye, A.W. Kyaw, E.Wee, C. Lee: Full/Part-time employment: Vela Research Singapore Pte. Ltd.

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e-Poster Display Session (ID 87) Poster Display

315P - High-penetrance breast and/or ovarian cancer susceptibility genes in Filipinos (ID 402)

Presentation Number
315P
Lecture Time
09:00 - 09:00
Speakers
  • Frances Victoria F. Que (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer is the most common cancer seen in women worldwide. In the Philippines, 24,798 cases of breast cancer were diagnosed in 2018, making up 17.6% of 141,021 newly diagnosed cases of cancer in the country. Genetic counseling and testing for hereditary cancers is a relatively new undertaking for medical oncologists in the Philippines. Previous studies show that prevalence of BRCA mutations in Filipinos is 5.1% to 6.8%, which is consistent with data found in the Asian population. However, no studies have yet been done looking at multigene panel testing for Filipino patients who meet the testing criteria for high-penetrance breast and/or ovarian cancer susceptibility genes.

Methods

From September 2019 to May 2020, we did multigene panel testing (Invitae Multi-Cancer Panel) for patients who met the testing criteria for high-penetrance breast and/or ovarian cancer susceptibility genes (NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020 – December 4, 2019). We tested 24 patients (23 females, 1 male; 29-81 years old), including 14 with breast cancer, 4 with ovarian cancer, 1 with both breast and ovarian cancer, 2 with pancreatic cancer, and 3 with no cancer but strong family history.

Results

Among the 24 patients tested, none had pathogenic BRCA1/2 mutations. However, one (4%) had a pathogenic PALB2 mutation (c.757_758del (p.Leu253Ilefs*3)), fourteen (58%) had one or more variants of uncertain significance (ALK, ATM, BARD1, BRCA2, CDKN1B, EGFR, KIT, MSH2, MSH6, MUTYH, NF1, NTHL1, POLE, RAD51D, RECQL4, SDHA, SDHB, SMARCA4, SMARCB1, TSC1), and nine (38%) had negative results.

Conclusions

As cancer genetics becomes more mainstream, use of multigene panels has been increasing, and cost of testing has been decreasing, making this more accessible to the average Filipino cancer patient. This is the first study to document the presence of other high-penetrance breast and/or ovarian cancer susceptibility genes in Filipinos. However, more research has to be done as we still do not know all the genes that may cause hereditary breast cancer and use of multigene panels increases the rates of detecting variants of uncertain significance and other incidental findings.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

F.V.F. Que: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self), Travel/Accommodation/Expenses: Camber Pharmaceuticals; Honoraria (self): Global Medical Technologies; Travel/Accommodation/Expenses: Astellas.

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e-Poster Display Session (ID 87) Poster Display

316P - Implementation of Vela Analytics to accelerate comprehensive interpretation and reporting of next-generation sequencing-based oncology testing in clinical diagnostic laboratories (ID 813)

Presentation Number
316P
Lecture Time
09:00 - 09:00
Speakers
  • Yingnan Yu (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Next-generation sequencing (NGS)-based diagnostics have demonstrated clinical utility in predicting survival benefits of targeted treatments in various cancer types. Tertiary analysis is a critical component in NGS workflow, but its efficiency and accuracy have remained as the main challenges. Herein, we developed Vela Analytics, a web-based software, that automates NGS data interpretation and reporting to facilitate timely clinical decision-making.

Methods

Clinical samples and commercial reference standards were analyzed using OncoKey SL60/525 Plus assays. The sequencing files were then analyzed using Vela Analytics, which utilizes the Vela Knowledge Base integrating information from FDA/EMA-approved labels, NCCN/ESMO-established clinical practice guidelines, registered clinical trials, and public data sources. Reports were generated through matching variants with the Knowledge Base.

Results

Reporting and interpretation of SNVs, INDELs, CNVs, fusion genes, MSI, TMB and oncogenic pathogens from OncoKey Plus assays were completed within 2-10 minutes. Fourteen actionable variants with 13 matched therapies and 185 clinical trials were identified in C3 reference standard (Horizon) and categorized into Tier I based on their strong clinical significance. Two immunotherapies were recommended based on MSI-High and TMB-High statuses detected. Reporting of therapies was customized for regions following ESMO or NCCN guidelines. The software interpreted HPV 16 findings in a head and neck sample with its clinical implications. There were no approved therapies targeting the detected variant PIK3CA R88Q. However, 11 active matched clinical trials suggested possible treatment benefits from investigational therapies.

Conclusions

Vela Analytics can efficiently and accurately provide clinical insights through identifying actionable genomic alterations and oncogenic pathogens, reporting up-to-date therapies and clinical trials, providing comprehensive literature interpretation, and categorizing variants according to AMP/ASCO/CAP guidelines.

Legal entity responsible for the study

Vela Genomics.

Funding

Has not received any funding.

Disclosure

Y. Yu, O. Scully, T. Zhang, Z.H. Kyaw, V.Y. Chung, D. Tay, C. Lee, P. Ariyaratne, M.K.K. Aye, M.Q. Yee, Y.L. Kok, E. Wee, C. Lee: Full/Part-time employment: Vela Research Singapore Pte. Ltd.

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e-Poster Display Session (ID 87) Poster Display

317P - Genomic profiling and molecular pathology of Chinese glioma patients (ID 799)

Presentation Number
317P
Lecture Time
09:00 - 09:00
Speakers
  • Yuanli Zhao (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Molecular characteristics are essential for the classification and grading of glioma. However, the majority of current understanding is based on public databases that might not accurately reflect the Asian population. Here, we studied the genetic landscape of Chinese glioma patients in hope to provide strong rationales for future molecular classification and prognosis of glioma.

Methods

Tissue samples from 81 glioma patients of which 21 (26%) were astrocytoma (A) and oligodendroglioma (O), 16 (20%) were anaplastic astrocytoma/oligodendroglioma (AO/AA), 32 (40%) were Glioblastoma (GBM), and 8 (10%) were diffuse midline glioma underwent next-generation sequencing with Acornmed panel including 808 cancer-relevant genes.

Results

We identified currently established molecular pathologic markers of glioma, including TP53 (41%),TERT (34%), IDH1/2 (30%), PTEN (19%), ATRX (18%), EGFR (16%), H3F3A (10%) and BRAF (6%). IDH mutations were frequent in A and O and were a major discriminate of biologic class (P=0.002). IDH-mutant A/O (grades II) were characterized by MGMT methylation, ATRX, and CIC mutations. AO/AA (grades III) were also IDH1/2-mutant, but instead are characterized by TP53, BRAF, and FUBP1 mutations. GBM typically lacked IDH1/2 mutations and demonstrated EGFR, PTEN, TP53, PIK3CA, and CDKN2A alterations, and TERT promoter mutations. Copy number variations as EGFR, PDGFRA, MET, KIT, which were also significantly associated with GBM but not used for clinical classification (P=0.001). Clinically actionable genetic alterations were detected in 80.95%, 81.25%, and 93.75% of A/O, AA/AO, and GBM, respectively.

Conclusions

We demonstrate that genes characterize the distinction between these pathologic subsets. These results further define molecular subsets of gliomas which may potentially be used for patient stratification and suggest potential targets for treatment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Li, H. Cheng, H. Wang, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

SARS-CoV-2 and cancer (ID 1155)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

320P - Psychometric interplay of the perception of the real-life impact of COVID-19 pandemic: A cross-sectional survey of patients with newly diagnosed malignancies (ID 912)

Presentation Number
320P
Lecture Time
09:00 - 09:00
Speakers
  • Kelvin Bao (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients newly diagnosed with malignancies amidst the COVID19 pandemic outbreak face the psychological double whammy of a gruesome diagnosis and a public health crisis. We conducted a cross-sectional survey to examine the association between common psychological disorders and cancer patients’ perception of COVID19’s real-life impact.

Methods

Newly diagnosed cancer patients were surveyed with a two-part questionnaire constructed by oncologists and clinical psychologists. It first explored patients’ perceptions of pandemic’s impact on cancer care resources, treatment quality, health-seeking behaviour and other concerns. The second part involved the measurement of post-traumatic stress disorder (PTSD) (abbreviated PCL-5), anxiety and depression (emotion thermometer) and intolerance to uncertainty (IUS12), where patients were assigned into high and low-risk groups accordingly. Their associations were observed and analysed using chi-square test.

Results

103 new cancer patients in Hong Kong were surveyed in May 2020. Results revealed there were more worries about the impact of COVID19 on cancer care manpower, and secondly about risk of infection during OPD waiting time, in patients of high risk group for PTSD (p= 0.011; p=0.015 respectively), anxiety (p=0.013; p=0.034), depression (p=0.017; p=0.043) and uncertainty tolerance (p=0.004; p=0.044). High IUS12 score was associated with more worry on pandemic’s impact on progress of cancer research and drug development (p=0.03). Patients of the high anxiety risk group were less likely to accept hospital’s “no visitor” policy during admission (p=0.013). High-risk group for anxiety (p=0.024) and depression (p=0.044) tend to consider the availability of media information on COVID19’s impact on cancer as inadequate. Patients of high PTSD risk group showed greater fear of being infected by family/carers (p=0.005).

Conclusions

This original survey revealed the potential value of psychometrics in understanding cancer patient’s perception of COVID19’s impact and predicting particular concerns in patients with different psychological phenotypes, allowing better-tailored pandemic time cancer care.

Legal entity responsible for the study

The authors.

Funding

Kowloon Central Cluster Research Committee Research Grant 20/21, Hospital Authority, Hong Kong, China.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

321P - Impact of COVID-19 and lockdown on adherence to treatment schedule among cancer patients (ID 579)

Presentation Number
321P
Lecture Time
09:00 - 09:00
Speakers
  • Krishnamani Kalpathi (Hyderabad, Andhra Pradesh, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The COVID-19 pandemic, detected first in December 2019, has led to four lakh deaths and close to 12 million being infected. It has led to disruption in mobility and access to healthcare due to measures such as social distancing and lockdown. Due to the infection, patients had difficulty to access transport facilities, interstate travel and obtaining permissions from authorities. All these factors led them not to adhere to their fixed appointments leading to an impact on outcome. Hence, with a collaborative effort from Oncologists and nursing staff, we explored the impact of COVID-19 and the lockdown on adherence to treatment among Cancer patients.

Methods

From April 1 to June 30, 2020, patient information was collected at the Day Care Unit, in the Department of Medical Oncology and Haematology at the American Oncology Institute, Serilingampally, Hyderabad, India. Patients with delay in treatment for more than 7 days were identified and followed up. Length of delay of treatment was recorded. All patients gave their informed consent for the study.

Results

A total of 737 patients underwent treatment. Number of patients who received treatment as per schedule were 656 (89%). Eighty-one patients out of a total of 737 (11%) during the 3-month COVID-19 period had treatment delays. Of these most treatment delays were due to fear of COVID infection (50.6%), followed by medical delays (26%) and transport and travel issues (23.4%). Impact of COVID per se on treatment delays was as low as 8%. A delay of 3- 7 days is usually acceptable for re initiating chemotherapy, to allow clinical and count recovery. Any delay beyond 7 days was considered nonadherence to treatment schedule. Most delays were shorter, less than 14 days (68%). Most of the delays were in the elderly age group (more than 50 years). Among patients missing their schedule, those more than 50 years and less than 50 years were 75 and 6 patients respectively. This was assessed in view of the increased mortality due to COVID in elderly patients.

Conclusions

Despite the pandemic and subsequent nationwide lockdown, treatment nonadherence due to COVID-19 was low, short and mostly seen in the elderly group. Cancer patients tend to continue treatment despite the COVID crises, and this requires validation in a longitudinal cohort.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

322P - Challenged faced by cancer patients during the COVID-19 pandemic (ID 765)

Presentation Number
322P
Lecture Time
09:00 - 09:00
Speakers
  • Mithra Krishnamani (HYDERABAD, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The COVID-19 pandemic has affected more than ten million people worldwide with nearly four lakh deaths. Cancer patients requiring continuum of care are facing difficulty accessing healthcare. Due to the risk of infection with COVID-19, their treatments have been rescheduled, elective procedures postponed, intravenous chemotherapies transitioned to oral medications, where possible, maintenance therapies deferred, and supportive care administered at home. Hence, we conducted a survey from the hospital patient registry to provide critical, up-to-date information about the impact of COVID-19 on cancer patients.

Methods

Patients taking treatment in the Department of Medical Oncology and Haematology at the American Oncology Institute, Hyderabad were given an online questionnaire upon consent. Details included age, cancer type, disease stage, treatment phase, delay in hospital appointment, procuring essential drugs including pain medicine, investigations, average time delay, impact on mental health, interpersonal relationships, deferring treatment due to fear of infection amongst other questions. Survey is also available in the local language besides English.

Results

A total of 200 patients participated in the survey with majority in the age group of 26-75 years (95.5%), 60% being female and the commonest cancers being breast (22%) and lung (16.5%) respectively. Patients receiving chemotherapy and immunotherapy were 58% and 3.9% with most being stage 3 (29%) and 4 (48.5%). Treatment delays were faced by 32% for various reasons while mental health impact in 67% patients. Majority of the patients expressed being at higher risk from COVID-19, with 35.8% agreeing upon continuation of chemotherapy and 66% preferring transition from injectable to oral medication. Forty five percent were aware of COVID-19 prophylaxis, while 85% discussed continuation or deferring treatment with their respective care giver.

Conclusions

This survey was a cooperative effort across many physicians, nurses and patients to provide critical, up-to-date information about the impact of the COVID-19 pandemic on cancer patients. Completing this short 10-minute survey or questionnaire will help health care to identify COVID-19 related issues in the community.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

323P - Oncology care in the Republic of Kazakhstan during COVID-19 (ID 1037)

Presentation Number
323P
Lecture Time
09:00 - 09:00
Speakers
  • Dilyara Kaidarova (Almaty, Kazakhstan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The new pandemic SARS-CoV-19 requires a new strategy in the oncology care in all over the world. Kazakhstan, with a population of 18.2 million, is a first country that re-introduced restrictions due to an increased level of the infected population. According to new rules, all admissions to the oncology hospitals and special care are based on negative RT-PCR tests and with no radiological evidence of pneumonia.

Methods

Patients with confirmed COVID-19 infection with clinical symptoms are treated in accordance with the National Guidelines of the COVID-19 management by Joint Commission on Quality of Health Services, Ministry of Health of the Republic of Kazakhstan. For these patients, special oncology treatment should be postponed. Special care of the SARS-CoV-2 symptoms is provided in infectious hospitals. As for July 21, there are 71,838 of the COVID-19 cases registered in Kazakhstan, put of which 3,585 are mortal ones. According to the National Cancer Register, there are 187,856 cancer patients in Kazakhstan. In order to evaluate the number of the oncological patients with COVID-19, we received data from the National Electronic Database in the period from March 2020 to July 2020.

Results

The total number of the infected cancer patients is 178 and it varies in different regions. The majority of the cases are registered in the Karaganda region with 43 cancer patients (24%), Nur-Sultan city - 19 cases (10.6%), and the Kostanay region -16 cases (9%) with the total numbers of the COVID-19 infected population in these regions of 7,401; 8,832 and 2,071 cases respectively. Overall in Kazakhstan, the total number of the deceased from COVID-19 patients with cancer registered is 14. In the Karaganda region there are 6 deceased patients, 2 - in Kostanay, 2 - in Kyzyl-Orda, and 2 – in the North-Kazakhstan regions.

Conclusions

We consider all the cancer patients as a risk group, due to the COVID-19 infection, however, we stratified patients with cancer into three following categories: patients who require immediate special treatment; patients, to whom special treatment can be postponed; and those who can be supervised distantly and for who special treatment is not required for up to 3 month.

Legal entity responsible for the study

Kaidarova Dilyara.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

324P - COVID era: Perception of oncologists from a developing nation (ID 405)

Presentation Number
324P
Lecture Time
09:00 - 09:00
Speakers
  • Rakesh Roy (Kolkata, West Bengal, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Cancer being a lethal disease, delay in treatment may be fatal. International organizations have come up with useful guidelines for cancer management. Still the availability of resources, infrastructure, state health policy, COVID incidence and approach of healthcare professionals differ. This study aims to find out the perception and approaches of Indian oncologists - which might prove to be useful in nation specific delivery of cancer care during COVID Pandemic.

Methods

After taking consent, a survey form was circulated online amongst oncologists (haemato/ radiation/ medical/ surgical) across the country and responses collected.

Results

79.2% oncologists represent private sector, 16.8% government sector. 50% oncologists were willing to postpone investigations for stable cancer patients. 42.6% willing to start treatment without knowing the COVID status, while 44.6% were against the idea and 12.9% were indecisive. 73% willing to perform surgery right away for operable nonemergency cases with a negative COVID status and rest 27 % willing to postpone surgery. Concurrent Chemoradiation (57%) was preferred over sequential approach (43%). Majority (53.5%) were comfortable prescribing chemotherapy via telemedicine. Asymptomatic COVID positive patients requiring chemotherapy 64.4% were willing to wait for the virus to resolve and then start therapy and 35.6% were suggesting some form of oral therapy and ongoing isolation. 89.1% preferred oral route if option present. 83.7 % preferred targeted therapy, 8.2% immunotherapy and rest went for other options. 93.1 % preferred day care chemotherapy during COVID and not admission. 61 % thought extended course of dexamethasone given as premedication during chemotherapy did not have a protective role for patients during COVID outbreak. Treatment initiation criteria in descending order - 39.6% stage of the disease, 36.6 % performance status, 22.8% COVID status and for rest it was the cost. 91% oncologists thought nurses were at a higher risk of exposure to COVID infection than the doctors. 54.5% were not taking anti COVID prophylaxis..

Conclusions

Greater homogeneity in practice was noticed amongst oncologists of a developing nation during COVID outbreak. The above information might be useful in policy making.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

325P - Clinical characteristics and outcomes of cancer patients with COVID-19 infection: A retrospective study in a single center in the Philippines (ID 593)

Presentation Number
325P
Lecture Time
09:00 - 09:00
Speakers
  • Frances Victoria F. Que (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The COVID-19 pandemic is a rapidly evolving crisis worldwide. Cancer patients represent a highly vulnerable group during this pandemic and are facing the most severe and critical consequences of this outbreak. This study aims to present our local data and contribute to our existing knowledge on the clinical impact of this novel disease on cancer patients.

Methods

We conducted a retrospective, single center, cohort study of cancer patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted in a tertiary hospital in Quezon City, Philippines from March to May 2020. Clinical characteristics, laboratory data and treatment histories were compared between patients with mild and severe outcomes. Chi-square test and Fisher’s exact test were applied to analyze the differences between groups.

Results

Nineteen cancer patients with COVID-19 infection were included. The most common tumor types were breast (26.3%), lung (21%), and genitourinary cancer (10.5%), and majority had early stage cancer (63.2%). Fifteen patients (78.9%) had recent anti-cancer treatment within 2 weeks prior to admission, most commonly, cytotoxic (21.05%) and targeted therapy (21.05%). Among patients who developed severe outcomes, most had lung cancer, stage IV disease, recent anti-cancer treatment, and higher levels of inflammatory markers. Findings of bilateral opacities on chest x-ray (p=0.009) and ground glass densities on chest CT scan (p = 0.002) were significantly associated with having severe complications. Having nosocomial-acquired infection was also associated with severe outcomes (p=0.004).

Conclusions

We found that those with recent anti-cancer treatment, particularly chemotherapy, have higher rates of severe complications; and that hospital-acquired infection is common among cancer patients and is associated with severe illness. Our study is limited by its small population, though our findings are consistent with other published studies. Our findings suggest that cancer patients require urgent and special attention during the pandemic, especially those who are receiving anti-cancer treatment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

326P - Management of diffuse large B cell lymphomas in the COVID-19 era (ID 630)

Presentation Number
326P
Lecture Time
09:00 - 09:00
Speakers
  • David Z. Ng (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients with haematologic malignancies, including diffuse large B cell lymphoma (DLBCL), have the highest COVID-19 severity and mortality. It is thus important to balance minimising nosocomial COVID-19 transmission with treatment of aggressive DLBCL. At the National Cancer Centre Singapore (NCCS), we implemented these changes: 1. Reduce outpatient visits for patients on surveillance through telemedicine consultations 2. Low threshold for prophylactic granulocyte stimulating factors (GCSF) to reduce febrile neutropenia 3. Low threshold for antimicrobial prophylaxis 4. Subcutaneous instead of intravenous rituximab to reduce “chair time” in suitable patients 5. Outpatient chemotherapy where possible (including for rituximab with dose-adjusted etoposide, prednisone, vincristine, doxorubicin and cyclophosphamide; DA R-EPOCH for double/triple hit lymphomas) 6. Central Nervous System International Prognostic Index (CNS-IPI) to determine high risk patients requiring CNS prophylaxis; delay CNS prophylaxis with intravenous methotrexate (MTX) to later cycles We then reviewed the data to see if these outcomes had been achieved.

Methods

Data from DLBCL patients between 1 March to 30 April 2019 and the same period in 2020 were reviewed retrospectively and compared. Statistical analysis was performed using the chi-square test (Stata version 16.0, StataCorp, Texas, USA).

Results

There was no nosocomial COVID-19 infection. Inpatient admissions and outpatient visits showed numerical decrease, with significant reduction in surveillance visits (p<0.001). Patients still received appropriate curative treatment. CNS prophylaxis was given when indicated; MTX was given intrathecally during staging lumbar puncture and intravenously later. Most on treatment received GCSF as primary prophylaxis. All who received R-EPOCH also received antimicrobial prophylaxis. There was no difference in number of patients receiving radiation or palliative care.

Conclusions

In- and outpatient visits were successfully reduced with no compromise to treatment and supportive care, with no nosocomial transmission of COVID-19. With no end from the pandemic in sight, this strategy for the management of DLBCL is useful in the “new normal” and for future pandemics of similar nature.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

327P - COVID-19 in patients with oncohematologic diseases in Kazakhstan (ID 1026)

Presentation Number
327P
Lecture Time
09:00 - 09:00
Speakers
  • Zaure Dushimova (Almaty, Kazakhstan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

SARS-CoV-2 is a novel coronavirus of zoonotic origin that emerged in China and now is spreading worldwide. 71 838 cases have been registered in Kazakhstan. At the moment, 3 585 of which died. The risk of coronavirus infection in oncohematological patients is much higher, due to a reduced immune status and immunosuppressive therapy, which they receive, as well as comorbidity in majority of patients.

Methods

We included all consecutive adult patients with oncohematologic diseases admitted to KazIOR, the Hematology Department, with laboratory-confirmed COVID-19 infection between June 15 and July 15, 2020. A confirmed case of COVID-19 was defined by a positive result on a real-time RT-PCR assay and radiological evidence of pneumonia CT-scan.

Results

The median patient age was 49 (range, 18–81) years, 64% were male. The median duration of symptoms before the COVID-19 PCR assay was was 4 (range, 0–22) days. Multiple myeloma (MM) was eleven patients, Acute Lymphoblastic leukemia (ALL)-three patients, Non-Hodgkin lymphoma (NHL)-three patients, Hodgkin Lymphoma (HL)-five patients, Chronic Lymphocytic leukemia (CLL)-two patients. 16 from 25 patients (64%) received chemotherapy at the time of COVID-19 diagnosis, which was registered during the treatment or after that. 13 patients had clinical symptoms, such as fever (n = 56%), cough (n = 25.8%), and shortness of breath (n = 48%), twelve patients were asymptomatic. CT scan of the chest was performed in 14 patients and bilateral ground glass opacities were evident in all cases. Five patients died, among them three patients died from the acute respiratory distress syndrome (ARDS), two patients with ALL had a progression of the process during chemotherapy, which was aggravated by the ARDS syndrome and acute renal failure.

Conclusions

Despite positive COVID-19 status patients with oncohematologic diseases require urgent specific treatment. The virus SARS-CoV-2 worsens the condition of comorbid patients, the response to treatment, increases the possible emergence of resistant and refractory patients, due to the lengthening of the inter-course periods. Risk factors as older age, and comorbidities such as diabetes, hypertension, or cardiac disease can aggravate patient condition which were confirmed by scientific research data.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

328P - Impact of COVID-19 pandemic on 30 days colorectal cancer patients mortality undergoing emergency operation (ID 882)

Presentation Number
328P
Lecture Time
09:00 - 09:00
Speakers
  • Ida Bagus Budhi (Surakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

During this COVID-19 pandemic we must face to the increasing emergency presentation of colorectal cancer patients, especially in the referral hospital. Many studies recommended that emergency laparotomy was safe with universal precaution during this pandemic and increasing morbidity-mortality rate. For emergency cases, the gold standard RT-PCR for COVID-19 was not feasible in this scenario, we must depend on rapid test for the screening. The two most common presentation of emergency colorectal cancer patients is laorge bowel obstruction and intestinal perforation. There were lack of data which already described about the impact of this pandemic on the short term outcome. Study reported the mortality and complication rate of emergency operation are 20-40% respectively.

Methods

This is a prospective study in academic hospital (Moewardi General Hospital, Indonesia) during the COVID-19 pandemic as one of the referral hospitals. The study started from March until June 2020, all patients with emergency laparotomy colorectal cancer patients will be included, the patients whose could not tolerated for emergency operation or found death on table (DOT) will be excluded. The main outcome for this study are post-operative morbidity and 30 days mortality.

Results

During this 3-month period, 35 patients were included on this study, 29 patients had large bowel obstruction due to colorectal cancer and the rest had diffuse peritonitis from intestinal perforation. 15 patients had sepsis condition according to current sepsis guidelines. 1 patient on intestinal perforation has been reported with positive rapid test result. Post-operative pneumonia has been found in 3 patients with intestinal perforation and could not survived during this study, the others of 2 patients had prolonged sepsis. Primary resection can be done on 30 cases with sigmoid colon was the most common site.

Conclusions

Emergency operation during this pandemic for colorectal cancer patients did not increasing the 30 days mortality but has an impact on post-operative pneumonia especially on intestinal perforation. Keywords: COVID-19 pandemic, emergency colorectal cancer, 30 days mortality

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

329P - Radiotherapy palliative and COVID-19: Experience of radiotherapy oncology department of Cancer Center Tlemcen, Algeria (ID 914)

Presentation Number
329P
Lecture Time
09:00 - 09:00
Speakers
  • Asma Mous (Tlemcen, Algeria)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The first patient infected with the COVID-19 virus in Algeria was reported on February 25, 2020. Radiotherapy departments are potentially exposed like others to the COVID-19 pandemic and this is a crucial issue since cancer patients cannot interrupt their treatment. The objective of this study is to describe the different epidemiological and therapeutic aspects of patients treated with palliative radiotherapy at the time of COVD-19.

Methods

It is a prospective study of the files of 28 patients treated aimed palliative at the radiotherapy department of the cancer center Tlemcen, Algeria since the new guidelines of our department to contain the spread of the pandemic from March 19 to April 30.

Results

They are 19 men and 9 women (sex ratio 2.11) with a median age of 61 years (35-87). 13 patients (46.42%) had brain metastases, six patients (21.42%) had bone metastases, two patients (7.14%) had esophagus, two patients (7.14%) had maxillofacial metastases and five (17.87%) patients had other localizations (lung, thyroid, sarcoma, multiple myeloma and glioblastoma). 30GY protocol was delivered in six (21.42%) patients, 20GY protocol was delivered in 16 (57.14%) patients and 8GY protocol was delivered in five (17.87%) patients.11 cases (84.61%) of brain metastases were treated with 20GY, five cases (83.33%) of bone metastases were treated with 8GY. No cases were infected with the virus.

Conclusions

Palliative radiotherapy plays a critical role in preventing serious morbidity in cancer patients even in the midst of the current COVID-19 pandemic. The acute phase of the pandemic has led to major changes in radiotherapy treatment strategy, including the use of hypo-fractionated regimens for palliative radiotherapy, which are preferred to reduce patients' risk of exposure to COVID-19 and to limit treatment delays. Hypo fractionation is one option that could at least partially address these issues.

Legal entity responsible for the study

A. Mous.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

330P - COVID and cancer: Choosing between hammer and anvil (ID 993)

Presentation Number
330P
Lecture Time
09:00 - 09:00
Speakers
  • Ullas Batra (New Delhi, Rohini, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The global Covid Pandemic has changed the world in last 6 months. The medical, social and logistic effects of the pandemic have been enormous. Many countries including India were put in absolute lockdown to prevent the transmission of this deadly virus. Cancer patients were precariously placed with the effect of lockdown as their immunocompromised status predisposed them to complications due to Covid while if they follow the lockdown, they were at increased risk of disease progression. This is an retrospective study from a tertiary Cancer Institute in Delhi, India which analyses the outcomes of COVID positivity in cancer patients undergoing treatment.

Methods

35 patients undergoing treatment for various non hematological malignancies and who were detected Covid positive by RT PCR were analysed. The time period was between April 2020 and June 2020.

Results

35 patients were analysed. 10 patients had NSCLC while 7 patients had ca breast.Remaining all patients had various non hematological malignancies. Out of which 22 patients were managed on OPD basis and 13 patients required hospitalisation. Out of 13 patients, 3 patients required ICU care in view of severe symptoms. 2 patients died of the disease and superimposed Covid infections. Out of these, 1 patient had received chemo in the prior week whilst the other had progressive disease and GI perforation as the cause of the mortality. Chemotherapy was restarted in 15 of these patients while 2 patients also underwent surgery after recovery.

Conclusions

In our dataset, Covid infection was not associated with increased risk of mortality and morbidity in Cancer patients. Large scale collective data sets are required to confirm these findings. Our data indicates that Oncological treatment should continue as usual in Covid pandemic while taking appropriate precautions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

331P - The clock stopped with COVID-19 but continued ticking for cancer patients (ID 766)

Presentation Number
331P
Lecture Time
09:00 - 09:00
Speakers
  • Sasi Shanmugam Senga (London, United Kingdom)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has killed over five hundred thousand people and has infected over 13 million people across the world in over 200 countries. Cancer patients fall under the high-risk category and are susceptible to the SARS-CoV-2 infection given the need for frequent hospital visits.

Methods

In this study, I analysed data from 46 cancer patients who were affected with different types of cancers (Table) and continued to receive cytotoxic treatment between January 2020 till July 2020.

Summary of the types of cancer and the treatment regimen of the 46 patients

Type of cancer Number of patients Treatment regimen
Astrocytoma 1 Temodal + Bevacizumab
Breast 3 EC + T
Breast 8 EC + TC
Breast 4 EC + THP
Colorectal cancer 4 FOLFOX
Colorectal cancer 3 FOLFIRI
Colorectal cancer 1 FOLFOX + Bevacizumab
Ewing sarcoma 1 VCD/IE
Gastric cancer 4 FLOT
Gastric cancer 2 XELOX
Lung cancer 4 Docetaxel + Carboplatin
Lung cancer 1 Topotecan
Lung cancer 4 Etoposide + Carboplatin
Lung cancer 1 Docetaxel + Cisplatin
Osteosarcoma 1 OS99
Osteosarcoma 1 HD-MTX
Pancreatic cancer 2 FOLFIRINOX
Small bowel 1 FOLFOX

Results

All the 46 patients included in the study completed their cytotoxic regimen without developing SARS-CoV-2 infection between January till July 2020.

Conclusions

The results from the study led to the hypothesis that three factors which were common among the cancer patients included in the study namely, 1) the use of granulocyte colony-stimulating factor (G-CSF), 2) the use of dexamethasone and, 3) dysbiosis of microbiome among cancer patients might be potential reasons for evading the deadly SARS-CoV-2 infection, despite their compromised immune status and a high likelihood of repeated exposure during hospital visits in comparison to the healthy general population, who are less likely to visit hospitals during the pandemic. The study aims to provide an alternate perspective and instigate discussion over the continuation of providing cancer care amidst the pandemic.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Supportive care (ID 1156)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

337P - A prospective study about the quality of life and chemotherapy-induced peripheral neuropathy (ID 191)

Presentation Number
337P
Lecture Time
09:00 - 09:00
Speakers
  • Wala Ben Kridis (Sfax, Tunisia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of chemotherapy (CT) (19% to 85% of cases, depending on the type of CT). This complication can further affect patients' quality of life (QOL). The aim of our work was to assess the quality of life (QOL) of patients according to the occurrence or not of an CIPN during anti-cancer treatment.

Methods

This is a prospective study performed on patients with known neurotoxic CT (Oxaliplatin, Cisplatin, Taxanes, Vinorelbine and Vincristine). The survey was carried out over a period of one month (September 2019) on patients treated at the department of medical oncology in Sfax. We used the WHO classification as well as the DN4 score to diagnose and characterize CIPN. We used the EORTC QLQ-C30 questionnaire to assess the QOL according to the presence or not of an CIPN. We analyzed 5 areas of QOL in our patients physical functioning, daily functioning, social functioning, pain, insomnia and overall health.

Results

Seventy-three patients were included in the study with 46 women (63%) and 27 men (37%). The average age was 51.8 years [13-80 years]. The cancers mainly reported in our series were: colorectal cancers (26%), breast cancers (24.6%), nasopharyngeal cancers (15%), ovarian carcinomas (11%) and eso-gastric cancers (6.8 %). The disease was metastatic in 43 cases (58.9%). The most widely used CT drugs were Taxanes (28 cases: 38.35%) and Oxaliplatin (22 cases: 30.14%). Thirty-eight patients had CIPN (52.1%). The CIPN was classified according to the WHO classification as grades 1 and 2 in 63.2% and 36.8% of the cases, respectively. The DN4 Score was ≥ 4 in 31 cases. We found a statistically significant change in patients' QOL in the areas of physical functioning (p <0.0001), daily functioning (p = 0.007), social functioning (p = 0.021), pain (p = 0.024) and overall health (p = 0.013) in case of CIPN.

Conclusions

In our study, the prevalence of CIPN was 51.1%. This CIPN significantly impacted the QOL in the areas of physical functioning, daily functioning, social functioning, pain and overall health. This is consistent with data from the literature.

Legal entity responsible for the study

Local Committee of Habib Bourguiba.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

338P - Vitamin E in the treatment of chemotherapy and radiation-induced mucositis: A meta-analysis of randomized controlled trials (ID 589)

Presentation Number
338P
Lecture Time
09:00 - 09:00
Speakers
  • Michelle Joane E. Alcantara (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Mucositis is one of the most common oral complications arising in cancer patients receiving chemotherapy and/or radiotherapy. The pain and distress of mucositis can be enough to cause disability during the course of treatment. Vitamin E has been found to have antioxidant and free radical scavenging properties which can reduce inflammation. To date, vitamin E supplementation in the form of tablets or pastes have been tried with different levels of success in several trials, however, there is no clear recommendation for its use. This study was done to obtain a more precise estimate of the efficacy of vitamin E on radiotherapy and chemotherapy-induced mucositis, in the hopes of providing an easily available, inexpensive but effective treatment for this condition.

Methods

A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were utilized to identify randomized controlled trials (RCTs) dated until December 2019, investigating the efficacy of oral or topical vitamin E in reducing oral mucositis in cancer patients receiving chemotherapy or radiotherapy. Using the random effects model, pooled Odds Ratio (OR) with 95% confidence intervals (CI) were calculated in measuring the incidence of improvement or resolution of oral mucositis.

Results

Four RCTs were included (N=171). The pooled rate of mucositis resolution was significantly higher in the group treated with Vitamin E (84.7% vs 51.2%), with an odds ratio of 6.04 (95% CI 2.46-14.84, p < 0.0001). Heterogeneity between the studies was minimal (I2 0-20%). Vitamin E was well-tolerated and there were no severe adverse effects reported in the studies.

Conclusions

The results showed that vitamin E (topical or oral) was significantly associated with higher rates of improvement of oral mucositis among solid cancer patients who underwent chemotherapy or radiotherapy. Our results suggest that vitamin E can be considered a simple, non-toxic, yet effective therapy for oral mucositis. Subgroup analysis based on type and dose of vitamin E administration, type of anti-tumor treatment, and type of cancer can be done once with additional studies in the future.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

339P - Diclofenac versus tramadol for mucositis related pain in head and neck cancer patients undergoing concurrent chemoradiation: A phase III study (ID 147)

Presentation Number
339P
Lecture Time
09:00 - 09:00
Speakers
  • Vikas Talreja (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Oral mucositis related pain during CTRT in head and neck cancers is a common problem. Unfortunately, in spite of it being common, there is limited evidence for selection of systemic analgesic in this situation. Hence, this study was designed to compare the analgesic effect of an NSAID (diclofenac) versus a weak opioid (tramadol).

Methods

This was an open-label, parallel design, superiority randomized controlled study. In this study head and neck cancer patients undergoing radical or adjuvant chemoradiation, who had grade 1 or above mucositis (in accordance with CTCAE version 4.03) and had pain related to it were randomly assigned to either diclofenac or tramadol for mucositis related pain control. The primary endpoint was analgesia after the 1st dose. The secondary endpoints were the rate of change in analgesic within 1-week, adverse events, and quality of life.

Results

128 patients were randomized, 66 in diclofenac and 62 in tramadol arm. The median AUC for the diclofenac arm and the tramadol arm were 348.936 units (Range 113.64-1969.23) & 420.87 (101.97-1465.96) respectively (p=0.05619). Five patients (8.1%) in the tramadol arm and 11 patients (16.7%) in the diclofenac arm required a change in analgesic within 1 week of starting the analgesic (p=0.184). There was no statistically significant difference in any adverse events between the 2 arms. However, the rate of any grade of renal dysfunction was numerically higher in diclofenac arm (10.6% versus 4.8%, p=0.326).

Conclusions

In this phase III study, evaluating diclofenac and tramadol for CRIM pain, the analgesic efficacy of both analgesics was found to similar, but diclofenac was associated with a higher rate of renal dysfunction.

Clinical trial identification

CTRI/2016/09/007302.

Legal entity responsible for the study

Tata Memorial Hospital.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

340P - Omega-3 fatty acids for cancer cachexia in advanced non-small cell lung cancer: A meta-analysis (ID 612)

Presentation Number
340P
Lecture Time
09:00 - 09:00
Speakers
  • Alfredo V. Chua (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Cancer cachexia is a common debilitating weight loss syndrome in advanced cancer, particularly in lung cancer patients. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), because of their immune-modulating effects, have been used to improve the nutritional status of patients with cancer cachexia. This meta-analysis evaluated the effect of omega-3 fatty acids in change in weight and lean body mass or skeletal mass, and in health-related quality of life (HRQoL) scores in patients with advanced non-small cell lung cancer.

Methods

Electronic databases were extensively searched for randomized controlled trials investigating omega-3 fatty acids in cancer cachexia among patients with advanced non-small cell lung cancer. Unpublished literature was also searched through manual handsearching and accessing online databases. Two review authors independently evaluated the methodological quality of the trials and analyzed the data.

Results

Six trials (394 patients) were included in the analysis. Five trials assessed change in weight, while two trials assessed change in lean body mass or skeletal mass, and HRQoL scores (Global Health and Physical Functioning Subscales). There is a significant difference in change in weight (mean difference [MD]: 1.22, 95% CI: 1.05 to 1.38; ƶ: 14.49, p<0.01) and HRQoL scores (Global Health subscale [MD: 14.40, 95% CI: 9.22 to 19.59, ƶ: 5.44, p<0.01] and Physical Functioning subscale [MD: 10.38, 95% CI: 8.50 to 12.27, ƶ: 10.78, p<0.01]) favoring the omega-3 fatty acids group. However, there is no sufficient evidence to support the association of change in lean body mass or skeletal mass, and the said intervention (MD: 2.05, 95% CI: -0.55 to 4.66; ƶ: 1.54, p: 0.12).

Conclusions

Among patients with advanced non-small lung cancer with cancer cachexia, there is a significant increase in weight and HRQoL scores in the omega-3 fatty acids group. However, there is no sufficient evidence to support the association of change in lean body mass or skeletal mass, and the said intervention.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

341P - Relationship between muscle mass and quality of life in breast cancer patients who underwent chemotherapy (ID 789)

Presentation Number
341P
Lecture Time
09:00 - 09:00
Speakers
  • Andree Kurniawan (Tangerang, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lean body mass and low muscle mass are associated with survival, quality of life (QOL), and tolerance to treatment in cancer patients. Most early breast cancer patients were reported in overweight and obese nutrition status. There is still limited data evaluating the relationship between muscle mass and QOL in breast cancer patients, especially in early stages. The aim of this study is to examine the relationship between muscle mass and QOL domain in breast cancer patients before underwent chemotherapy.

Methods

A total of 80 breast cancer patients were enrolled in this study. Women breast cancer patients before they underwent chemotherapy were included in this study. Skeletal muscle mass was measured by bioelectrical impedance analysis, and it was reported as the Skeletal Muscle Index (SMI). QoL was assessed using the EORTC-QLQ-C30. The correlation between SMI and QOL was evaluated using Pearson or Spearmen correlation test based on the normality data.

Results

The mean of age was 47.39+7.07 years old. The median of body mass index (BMI) was 23.15(7.86-47.26) kg/m2. The distribution of BMI for underweight, normo-weight, overweight and obese were 5(6.3%); 33(41.3%); 16(21.1%); and 26(32.6%), respectively. Most patients were in early breast cancer 71 of 80 (88.8%). The median of SMI was 5.72(1.91-12.35). The median of QOL global health status, physical function, role function, emotional function, cognitive function, and social function domain were 66.67(0-100); 93.33(0-133.33); 100(0-133.33); 83.33(33.33-100); 100(16.67-100); and 100(0-100), respectively. The correlation between SMI and QOL global health status, physical function, role function, emotional function, cognitive function, and social function domain were (r 0.194, p 0.085); (r 0.021, p 0.851); (r 0.009, p 0.939); (r 0.061, p 0.588); (r 0.280, p 0.012); and (r 0.078, p 0.490), respectively.

Conclusions

Almost all QOL domains of breast cancer patients before underwent chemotherapy showed good results. The relationship between muscle mass and QOL in breast cancer patients before underwent chemotherapy only showed in the cognitive domain. Further studies need to be done to evaluate the physical activity and protein consumption practice with QoL.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

342P - Comparison of 0.25 mg versus 0.75 mg of palonosetron in combination with aprepitant and dexamethasone for prevention of chemotherapy-induced nausea and vomiting following cisplatin-containing chemotherapy in patients with esophageal cancer (ID 944)

Presentation Number
342P
Lecture Time
09:00 - 09:00
Speakers
  • Satoshi Horasawa (Kashiwa, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Palonosetron (PALO) is a second generation 5HT-3 receptor antagonist recommended as a preferred drug for high-emetogenic chemotherapies. PALO 0.25 mg has been reported to be as effective as 0.75 mg with less adverse events, such as constipation, when used alone or in combination with dexamethasone (DEX). The efficacy and safety of PALO 0.25 mg compared to 0.75 mg in combination with aprepitant (APR) plus DEX in patients (pts) with esophageal cancer remain unclear.

Methods

We retrospectively evaluated the efficacy and safety of PALO 0.25 mg versus 0.75 mg in combination with APR plus DEX in pts with localized or metastatic esophageal cancer who received cisplatin (CDDP)-containing chemotherapy between Nov. 2015 and Mar. 2017 at our institution. Complete response was defined as no emetic episodes and no rescue medication use.

Results

This study enrolled 58 and 55 pts who received PALO 0.25 mg and 0.75 mg. The baseline characteristics were similar between both groups. Sixteen (28%) and 24 (44%) pts received triplet regimen (docetaxel, CDDP and 5-fluorouracil), respectively. The complete response rates were 72% for 0.25 mg and 62% for 0.75 mg, with no significant difference (odds ratio [OR] = 0.62, p = 0.23). Percentages of no nausea was also similar with 40% and 33%, respectively (OR = 0.74, p = 0.44). Grade 2-3 constipation and any grade of aspartate aminotransferase increase were more frequently observed in 0.75 mg group (38% vs. 58%, p < 0.05; 7% vs. 22%, p < 0.05). In univariate and multivariate analyses, no association between baseline characteristics, including dose of PALO, and complete response rate was observed. Meanwhile, PALO 0.75 mg, older age, localized disease, and tobacco consumption were significantly associated with grade 2 or more constipation (OR = 0.28, p < 0.01; OR = 0.28, p < 0.01; OR = 3.09, p < 0.05; OR = 0.27, p < 0.05).

Conclusions

PALO 0.25 mg in combination with APR plus DEX may contributed to the decrease in constipation in pts with esophageal cancer who received CDDP-containing chemotherapy without compromising the anti-emetic effect compared to 0.75 mg.

Legal entity responsible for the study

National Cancer Center.

Funding

Has not received any funding.

Disclosure

Y. Nakamura: Research grant/Funding (institution): Taiho Pharmaceutical. H. Taniguchi: Honoraria (self): Bayer; Honoraria (self): Sanofi; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self): Chugai; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Lilly Japan; Honoraria (self): Merck Serono; Honoraria (self): Yakult Honsha; Honoraria (self): MBL; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (self): Mitsubishi Tanabe Pharma; Honoraria (self): Nippon Kayaku; Research grant/Funding (institution): Sumitomo-Dainippon Pharma; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): MSD Oncology; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): Sysmex. T. Kojima: Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Astellas Amgen BioPharma; Research grant/Funding (institution): Chugaiseiyaku; Research grant/Funding (institution): Parexel; Research grant/Funding (institution): Shionogi; Advisory/Consultancy: Bristol-Myers Squibb Company; Advisory/Consultancy: Merck Biopharma; Honoraria (self): Oncolys BioPharma. T. Yoshino: Research grant/Funding (institution): Novartis Pharma; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Parexel International; Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): GlaxoSmithKline. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

343P - Head-to-head comparison of palonosetron versus granisetron for prevention of chemotherapy induced nausea and vomiting: Systematic review and meta-analysis (ID 183)

Presentation Number
343P
Lecture Time
09:00 - 09:00
Speakers
  • Chin-Yu Hsu (Taipei City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Palonosetron was greater than first-generation 5-HT3 receptor antagonists in the prevention of nausea and vomiting have been established in many systematic reviews. However, several recent randomized control trials manifested inconsistent results. Thus, we conducted a systematic review to evaluate the efficacy and safety of palonosetron versus granisetron in chemotherapy induced nausea and vomiting (CINV).

Methods

The PubMed, Embase, and The Cochrane Library databases were searched for studies published before April 2020. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcome was treatment responses of CINV (complete response rate, complete control rate, and total control rate). Secondary outcomes were 5-HT3 receptor antagonist related common side effects (constipation, and headache).

Results

Twelve randomized controlled trials, three prospective studies and one retrospective study were reviewed. Palonosetron was consistently statistically superior in any phase of complete response rate (acute phases: odds ratio [OR]= 1.37, 95% confidence interval [CI]: 1.03 to 1.82; delayed phases: OR= 1.57, 95% CI: 1.15 to 2.15; overall phases: OR= 1.37, 95% CI: 1.17 to 1.60), delayed phases of complete control rate and total control rate (OR= 1.45, 95% CI: 1.23 to 1.72; OR= 1.29, 95% CI: 1.01 to 1.65, respectively). Subgroup analysis indicated that there was no significant difference between palonosetron and granisetron in any phase of complete response when combined with NK1 antagonists. No statistically significant difference was found between constipation and diarrhea toxicities of the two groups.

Conclusions

Although palonosetron significantly decreased the risk of chemotherapy induced nausea and vomiting in any phase, granisetron is seeming comparable effectiveness with palonosetron when adding NK1 antagonists.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

344P - Single-centre analysis of anti-resorptive agent-related osteonecrosis of the jaw in lung cancer patients (ID 135)

Presentation Number
344P
Lecture Time
09:00 - 09:00
Speakers
  • Kohei Fujita (Kyoto, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Over the past two decades, anti-resorptive agent-related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real-world clinical setting. To our knowledge, we are the first to do so.

Methods

We retrospectively analysed lung cancer patients with bone metastases who had received anti-resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria.

Results

A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%), and three (23.1%) had adenocarcinoma, squamous carcinoma, and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of anti-resorptive agents (OR, 11.54; 95% CI, 2.47–53.99; P <0.01), and longer survival duration (≥2 years) (OR, 12.16; 95% CI, 3.17–46.65; P <0.01) were independently associated with ARONJ in a multivariate analysis.

Conclusions

The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using anti-resorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

345P - Thromboembolic events in brain tumour patients on bevacizumab (ID 779)

Presentation Number
345P
Lecture Time
09:00 - 09:00
Speakers
  • Gunjesh K. Singh (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Venous thromboembolism (VTE) is a common event in brain tumour patients. The risk is further believed to increase with the addition of bevacizumab. In view of limited literature addressing this issue, we found the need to conduct this study.

Methods

The database of the adult patients with primary brain tumour on bevacizumab therapy, was utilised to see the occurrence of VTE. The demographics were noted and Khorana score was calculated. Pearson correlation analysis was done and the Pearson correlation coefficient was estimated between Khorana score and VTE. P-value <0.05 was considered statistically significant.

Results

Out of 80 patients, 7 (8.8%) had VTE events after starting bevacizumab. It was diagnosed as deep vein thrombosis (DVT) in 4 (5%) patients and pulmonary thromboembolism (PTE) in 3 (3.8%) patients. Also, out of all, 43 (53.8%) patients belonged to the low risk category of Khorana score, while 37 (46.2%) patients were in the intermediate category. There was no significant association between Khorana scores obtained and VTE (fisher exact test, p-value = 0.171).

Khorana score and VTE

Khorana sore Venous thromboembolism (VTE)
Yes No
0 2 (4.7%) 41 (95.3%)
1 4 (12.1%) 29 (87.9%)
2 1 (25%) 3 (75%)
3 0 0
.

Conclusions

The incidence of VTE in primary primary brain tumour patients receiving bevacizumab therapy is low. Low and intermediate risk Khorana scores are unable to predict the risk of VTE in our population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

346P - Occurence and risk factors of chemotherapy-induced neutropenia in patients with breast cancer: A hospital-based assessment in Indonesia (ID 972)

Presentation Number
346P
Lecture Time
09:00 - 09:00
Speakers
  • Susanna H. Hutajulu (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy-induced neutropenia (CIN) is a main side effect in chemotherapy of breast cancer (BC) patients. It may lead to febrile neutropenia that requires hospitalization and antibiotic treatment resulting in increased cost and unfavourable outcome. Little is known about the incidence of CIN in Indonesia despite the fact that BC is the most prevalent malignancy. This study investigates the occurence of severe CIN and identify its associated risk factors.

Methods

We considered 123 newly-diagnosed BC patients without terminal conditions and multiple cormobidities from July 2018 to July 2019. All patients received a three-weekly adjuvant, neo-adjuvant, or palliative chemotherapy without primary prophylaxis of GCSF. We defined severe CIN as the condition where absolute neutrophil count <0.5x109/L during any chemotherapy cycle. We evaluated the association of clinical, pathological, and treatment factors with the risk of CIN in a logistic regression methodology, adjusted for patients’ demography.

Results

In this cohort, 73% patients had experienced severe CIN at least once during their chemotherapy. The risk of severe CIN in the 2nd, 3rd, and 4th cycle did not differ from the 1st cycle. However, after the 5th cycle, the risk significantly increased (p values ≤ 0.001 up to the 8th cycle). Higher age, poor ECOG index, lower pre-treatment monocyte count, and palliative intention were associated with the increased risk of severe CIN, while diabetes comorbidity was associated with the decreased risk (p= 0.049, < 0.001, 0.022, 0.037, and 0.017, respectively).

Conclusions

We have identified some risk factors for increasing the risk of severe CIN. These factors can serve as a guidance to support care and recognize those at high risk.

Legal entity responsible for the study

The authors.

Funding

The Indonesian Ministry of Research, Technology, and Higher Education.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

347P - Histamine blockade with loratadine for prevention of granulocyte-colony stimulating factor (G-CSF)-associated bone pain: A meta-analysis (ID 195)

Presentation Number
347P
Lecture Time
09:00 - 09:00
Speakers
  • Mel Valerie Ordinario (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy remains to be one of the cornerstones of cancer management. Due to the inherent ability of chemotherapy to act on rapidly dividing cells, myelosuppression is one of the noted side effects. Febrile neutropenia (FN), an oncologic emergency, may be prevented with administration of granulocyte-colony stimulating factor (G-CSF) in patients who are at risk for neutropenia based on type and number of myelosuppressive chemotherapy agents used, the type of cancer and patient-related factors. Most common adverse events are injection site and bone pain. Recent studies showed promising results on prevention of G-CSF induced bone pain using histamine blockade.

Methods

A systematic search of Pubmed, Cochrane, Clinical trials databases and hand search were done to identify randomized controlled trials (RCTs) investigating the use of Loratadine for prevention of G-CSF bone pain. Studies were appraised using the Cochrane Collaboration tool. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI), results were analyzed.

Results

Two RCTs were included ( N=814). Patients in the Loratadine group reported lesser bone pain as compared to the control group, 57% and 60% respectively (OR 0.95, CI [0.81, 1.10). However, the result was not statistically significant (P=0.52).

Conclusions

Histamine blockade with Loratadine in the prevention of bone pain induced by G-CSF did not show statistically significant advantage over placebo or no prophylaxis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

348P - Anti-VEGF inhibitors and renal safety in onco-nephrology consortium: Urinary protein/creatinine ratio (VERSiON UP study) (ID 463)

Presentation Number
348P
Lecture Time
09:00 - 09:00
Speakers
  • Michio Nakamura (Sapporo, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To investigate the clinical significance of urine protein quantitative test UPCR (ratio of urinary protein amount measured and creatinine concentration in urine) when anti-angiogenesis inhibitors are used.

Methods

From January 2018 to December 2018, a survey was conducted based on the medical records of gastric cancer and colorectal cancer cases with urine protein qualitative value test (QV) of 2+ or higher during the use of anti-angiogenesis inhibitors at 9 institutions participating in Onconephrology Consortium. The primary endpoint was the ratio of UPCR worst value less than 2 (Low UPCR) in QV 2+ cases. The secondary endpoints were comparison of Low UPCR and UPCR worst value2 or higher (High UPCR), the use status of angiogenesis inhibitors, changes in urine protein test values (qualitative/quantitative), subsequent treatment information, and patient background factors and other relationships.

Results

Among 71 cases enrolled, the proportion of Low UPCR in QV 2+ cases (n=53) was 66% (n=35). In a comparison between Low (n=36) and High UPCR cases (n=24), High UPCR tended to occur in cases of heavy body weight, and its cut-off value was 52.45 kg (OR 4.25, 95%CI 1.30-13.86, p=0.017). A significant correlation was also observed between UPCR levels and the single dose of bevacizumab (p=0.033) or ramcirumab (p=0.018).

Conclusions

The relationship between UPCR levels and body weight or single dose was shown, but there is a possibility that physical disparity and the amount of creatinine excretion may have an effect.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Nakamura: Honoraria (self): Daiichi Sankyo; Honoraria (self): Lilly; Honoraria (self): Chugai; Honoraria (self): Mochida; Honoraria (self): Bristol Myers Squibb; Honoraria (self): Taiho. T. Funakoshi: Research grant/Funding (institution), TF belongs to an endowed department sponsored partly by Chugai Pharmaceutical Co., Ltd.: Chugai. E. Baba: Honoraria (self): Lilly; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Chugai. Y. Mihara: Honoraria (self): Chugai. M. Muto: Honoraria (self), Research grant/Funding (institution), MM belongs to an endowed department sponsored partly by Chugai Pharmaceutical Co., Ltd.: Chugai; Research grant/Funding (self): Sanofi. M. Yanagita: Honoraria (self): Chugai; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): Tanabe Mitsubishi; Research grant/Funding (institution): Nippon Boehringer Ingelheim; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Baxter; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Takeda. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

349P - Proteinuria in patients treated with ramcirumab increases the risk of renal dysfunction (ID 170)

Presentation Number
349P
Lecture Time
09:00 - 09:00
Speakers
  • Kenta Hayashino (Kure, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

It is unknown whether proteinuria caused by ramcirumab (RAM) induces renal dysfunction. Thus, this study assessed the relationship between proteinuria and other factors with RAM therapy, and compared estimated glomerular filtration rate (eGFR) with or without proteinuria in long-term treatment.

Methods

Medical records were retrospectively reviewed for 156 patients treated with chemotherapy that included RAM between April 1, 2015 and May 31, 2019 at Kure Medical Center. Forty-eight patients with a performance status of 3 or 4, or not measured for proteinuria among those treated with RAM, or has detected proteinuria before first commencing RAM administration were excluded. Proteinuria and eGFR were measured before treatment with RAM, and compared to minimum eGFR with or without proteinuria after treatment with RAM. The proteinuria group was defined as proteinuria detected at more than 1+ at least once.

Results

Overall, a total of 108 patients were included in this analysis. Thirty-nine patients were classified into a proteinuria group and the remaining 69 patients were classified into the non-proteinuria group. Age, sex, and eGFR before treatment with RAM did not significantly differ between the proteinuria group and non-proteinuria group. There were significant decreases in proteinuria group mean eGFR(-26.7±5.6 ml/min/1.73 m3), which was greater than the non-proteinuria group mean eGFR(-15.0±4.2 ml/min/1.73 m3), compared to eGFR before treatment (p<0.05). The incidence of grade 3 or 4 chronic kidney disease (CKD) was observed in 8 patients (20.5%) in the proteinuria group, but in only 3 patients (4.5%) in the non-proteinuria group (p<0.05). Patients treated over 200 days with RAM had a significant incidence of proteinuria, and in the proteinuria group, the appearance of proteinuria within 28 days from first administration decreased eGFR more than after 28 days.

Conclusions

Proteinuria caused by RAM might be decreased in eGFR, particularly in cases that immediately detected. Renal dysfunction can affect subsequent chemotherapy, and as such, it is important to regularly check proteinuria during treatment with RAM. It is necessary to take particular care for cases in which proteinuria is detected and renal function has already declined.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

350P - Rheumatologic immune related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy: A Western Australia experience (ID 594)

Presentation Number
350P
Lecture Time
09:00 - 09:00
Speakers
  • Azim Khan (Nedlands, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immune checkpoint inhibitors (ICI) have demonstrated improvement in overall survival across a range of tumor types. However, ICI therapy is associated with severe immune related adverse events (irAEs) including inflammatory arthritis. Here, we report our experience for rheumatological irAEs in patients with and without pre-existing auto-immune disease (AID).

Methods

Data was collected retrospectively for 15 patients identified as having rheumatological irAEs secondary to ICI therapy in our center between 2015-2019. We identified three patients with pre-existing AID.

Results

The mean age of the cohort was 66 years.The commonest tumour types were melanoma (73%) and NSCLC (27%). In the group without AID, (n=12), 7 patients developed inflammatory arthritis (IA). Two patients with PMR like syndrome depicted typical clinical phenotypes supported by raised inflammatory markers. The SICCA syndrome patient had biopsy proven lichenoid drug eruption and feature of xerostomia. One patient had synovial aspiration proved OA exacerbation treated with intra-articular corticosteroid injection, ceasing ICI. One patient developed grade 3 immune mediated myositis 12 days after commencing nivolumab. Muscle biopsy showed active inflammatory myopathy and lymphocytic vasculitis. Median time to any rheumatologic irAEs was 9.8 weeks. Treatment was withheld temporarily in patient and it was stopped permanently in 2 patients. All patients had high doses of glucocorticoids that led to significant, moderate and minimal improvement in 2, 8 and 2 patients, respectively. Additionally, 3 patients needed other disease modifying anti-rheumatoid drugs (DMARDs). In cohort with pre-existing AID (n=3), only patient with rheumatoid arthritis (RA), had flare of RA after 7 weeks of initiating ICI therapy. ICI therapy was withheld and had resolution of symptoms with steroids.

Conclusions

Rheumatic irAEs are serious and less understood adverse events secondary to ICI therapy requiring steroids and additional immunosuppressive therapy. Future studies should aim at defining the type of rheumatologic irAEs experienced in trials patients and response to steroids +/- DMARDs. A mutli-disciplinary approach is recommended.

Legal entity responsible for the study

Dr. Azim Khan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

351P - Valvular heart diseases in patients treated for breast cancer (ID 784)

Presentation Number
351P
Lecture Time
09:00 - 09:00
Speakers
  • Ekaterina Kushnareva (Saint-Petersburg, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Aortic stenosis is the most common valvular complication of mediastinal radiotherapy. In 2016 was shown that not only radiotherapy but chemotherapy with anthracyclines alone may provoke the development of valvular heart diseases (VHD). But there are still not clear time frames of VHD development.

Methods

We present a single-center retrospective analysis of a cohort with breast cancer history who were treated in cardiology departments. Total 91 patients were included in this study. ECHO data and time till first symptoms and surgical treatment were assessed in all patients.

Results

Different VHD were revealed in 48.35% (n=44) of patients. Among them 54.5% (n=24) had aortic stenosis, 34.1% (n=15) – mitral regurgitation, 4.5% (n=2) – mitral stenosis with regurgitation, 2.3% (n=1) – isolated aortic regurgitation and the same number of isolated mitral stenosis. During 15 months 25 patients were undergoing surgical treatment. In 2 of them VHD was first diagnosed before cancer treatment, so they weren’t included in the subsequent analysis. The oncological age in operated patients was 60 [42; 68] years. The time till first signs of VHD was 8 [4; 16.5] years. In all patients dyspnea was presented, 39% of patients had angina and only in 21.7% had presyncopes and syncopes. The median time from oncological age till surgery was 11 [7; 22] years. We also revealed correlation between oncological age and time till first VHD signs and surgical treatment (r = -0.76 and r = -0.71 respectively).

Conclusions

Given the widespread prevalence of degenerative aortic stenosis in older age patients, it is advisable to assess valves condition not only before radiation and chemotherapy but also recommend more frequent echocardiographic monitoring after, as well as use of new visualization techniques, such as CT (calcium score) and 18F-NaF PET-CT (as marker of calcification).

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

352P - Reproductive system disorders following chemotherapy in patients with breast cancer in Yogyakarta, Indonesia (ID 985)

Presentation Number
352P
Lecture Time
09:00 - 09:00
Speakers
  • Irfan Haris (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Breast cancer (BC) and its treatment could disturb the reproductive system. We identified reproductive system disorders following chemotherapy in patients with BC and the determinant factors.

Methods

One hundred and twelve married female patients with BC who underwent first chemotherapy between 2018 and 2020 in Dr. Sardjito Hospital, Yogyakarta were recruited. Socio-demographic and clinical data were collected at baseline. After each chemotherapy session, the patients were interviewed about symptoms of reproductive system disorder (irregular menstruation, vaginal dryness, decreased libido, dyspareunia, delayed orgasm and anorgasmia) and other symptoms (fatigue, anorexia, nausea and anxiety). We used a questionnaire based on the CTCAE version 4. Data of symptoms were collected until patients received at least 3 treatment cycles. Chi square and Fisher’s exact tests were used to analyze any association among variables.

Results

The most common symptoms were vaginal dryness (41.1%) followed by decreased libido (39.3%). In the subgroup analysis, the most common symptom among 44 pre-menopause women was irregular menstruation (84.1%). Vaginal dryness occurred more in cases with anthracycline-based regimen (p=0.036) and with anxiety (p=0.019), compared to their counterparts. Decreased libido presented more in cases with younger age (p=0.037) and positive ER status (p=0.009). Irregular menstruation, dyspareunia, delayed orgasm, and anorgasmia did not correlate with any of the determinant factors.

Conclusions

Reproductive system disorders occurred very frequently in the local BC patients after receiving chemotherapy. Influencing factors included anthracycline-based regimen, anxiety, age, and estrogen receptor status.

Editorial acknowledgement

Erik Christopher Hookom, BA, M.Ed, TEFL Office of Research and Publication, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada.

Legal entity responsible for the study

The authors.

Funding

The Indonesian Ministry of Research, Technology, and Higher Education; Public Funding, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

353P - Survey for geriatric assessment in practising oncologists in India (ID 145)

Presentation Number
353P
Lecture Time
09:00 - 09:00
Speakers
  • Vikas Talreja (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To date, there is limited information on Indian oncologists' views and experiences of geriatric oncology. This study aimed to explore the views of Indian oncologists regarding the perception of, and barriers to the incorporation of geriatric screening tools, GA and collaboration with geriatricians in routine clinical practice.

Methods

This was an anonymized cross-sectional survey. The online survey, based on a literature review and expert opinion, comprised 12 questions covering: (i) respondent characteristics, clinical practice environment and patient population; (ii) challenges and treatment decision-making factors in the management of older patients with cancer; and (iii) benefits of and barriers to the implementation of GA or geriatrician review in cancer care for older patients. Qualitative variables were reported as numbers (N) and percentages. Statistical analyses were performed using χ 2 or Fisher’s exact test. Results were considered statistically significant with p < 0.05. Statistical analyses were conducted using SPSS software (version 20).

Results

Between March 2019 and June 2019, 100 answers were collected. Only 74 centres (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 100; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centres. Almost all (91%) claimed not to apply special management practices using specific tools for every geriatric patient. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved.

Conclusions

From the nationwide survey, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived.

Legal entity responsible for the study

Tata Memorial Hospital.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

354P - Knowledge, perception, and attitude of oncology-related healthcare providers on complementary and alternative medicine (CAM) (ID 273)

Presentation Number
354P
Lecture Time
09:00 - 09:00
Speakers
  • Chih Kiang Tan (Kuala Lumpur, Malaysia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In Malaysia, up to 68% of cancer patients uses CAM, with CAM disclosure at only 7.6%. Perception of doctors’ poor knowledge on CAM, and non-belief in its practice are some reasons cited for non-disclosure. This may lead to various complications.

Methods

This cross-sectional study was carried out in 2 university hospitals in Malaysia from 1st July to 23rd December 2016. All doctors and nurses of Oncology Departments were included. Subjects were briefed on the study before questionnaires were distributed and returned anonymously once completed. The questionnaire was adopted with local adaptations, from a study done in Japan on perceptions and attitudes on CAM. A pilot study was done and the final validated version consists of 2 sections. Section A consists of questions on socio-demographic characteristics of respondent. Section B consisted of questions to assess the respondent’s knowledge, perception and attitude on CAM. Each question was given a point scale. Based on total points obtained, respondents were classified into good or poor knowledge, positive or negative perception and attitude towards CAM.

Results

Total of 60 nurses and 26 doctors responded, with 16 male and 70 female. Generally, all respondents have poor knowledge on CAM. Two thirds (67.4%) were not aware of the existence of the National Policy on CAM in Malaysia. Most have very little or no knowledge on the CAM modalities listed. The respondents have negative perception on CAM, with 83.7% feel the lack of evidence in its effectiveness. Most (72%) think that there is a definite or possible interaction between CAM products and anticancer drugs. All have negative attitude on CAM except 8.1% of respondents encouraging the use of CAM. Majority do not encourage the use of CAM products in both early (79.1%) and advanced (64%) stage.

Conclusions

Oncology-related healthcare providers have poor knowledge, with negative perception and attitude towards CAM.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

355P - Impact of comorbidities and rurality on treatment commencement, completion and outcomes, and health related quality of life, for geriatric oncology patients: Preliminary findings from a regional Australian study (ID 792)

Presentation Number
355P
Lecture Time
09:00 - 09:00
Speakers
  • Mathew George (Tamworth, NSW, Australia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In Australia, 58% of cancer diagnoses and 76% of cancer mortality is in patients aged >65. Comorbidity increases with age, and both factors affect cancer treatment choices, initiation and outcomes, and health related quality of life (HRQoL). Rurality also impacts these experiences, however despite emerging evidence, rural geriatric oncology populations are underrepresented in available studies. This study therefore aims to determine the prevalence of physical comorbidities among this cohort, and to study the relationship between comorbidity, rurality, treatment process and outcomes, and HRQoL.

Methods

The study includes patients aged >65, with any solid tumour diagnosis, attending a regional cancer centre. Quantitative data was obtained using validated tools to examine HRQoL, comorbidities, and clinical parameters, with analysis of predictor variables to quantity association with comorbidity and rurality. Qualitative data was obtained via focus groups with patient, caregiver and health professional cohorts, with thematic analysis undertaken using iterative coding.

Results

Qualitative data highlighted factors influencing diagnosis and treatment, including: difficulty/cost of travel; and other impacts of living in a regional location. Diagnosis delay/complication and emotional aspects were identified as key to cancer experiences, and in HRQoL. Preliminary analysis of quantitative data collected to date (n=110) complements this, with 57% of patients classified as living in outer regional Australia, and 24% as inner regional. Around 30% had at least one comorbidity. A significant relationship does appear between rurality, comorbidities, and HRQoL. The relationship with treatment outcomes is less clear.

Conclusions

Preliminary analysis identifies several key challenges to treatment commencement and completion, including financial, logistical and emotional issues. Statistical analysis further indicates that both rurality and comorbidities may negatively impact HRQoL, and treatment commencement/completion. Data collection and analysis is ongoing to end 2020.

Legal entity responsible for the study

Hunter New England Local Health District - Tamworth Rural Referral Hospital.

Funding

Tamworth Hospital, Hunter New England Local Health District.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Thoracic tumours, early stage (ID 1157)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

357P - Comparison between immunotherapy and chemotherapy as neoadjuvant setting in resectable non-small cell lung cancer: A systematic review and meta-analysis of prospective trials (ID 319)

Presentation Number
357P
Lecture Time
09:00 - 09:00
Speakers
  • Chao Zhang (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors have preliminarily shown encouraging results as neoadjuvant setting. No data reported on randomized trials comparing neoadjuvant immunotherapy and chemotherapy leaving undetermined critical issues for better clinical treatment options.

Methods

We conducted a systemic review of trials involving neoadjuvant immunotherapy and chemotherapy, performing an indirect comparison meta-analysis of neoadjuvant immunotherapy and neoadjuvant chemotherapy upon multiple short-term outcome.

Results

This systematic review and meta-analysis included 10 trials of neoadjuvant immunotherapy and 11 neoadjuvant chemotherapy involving 1755 patients. Patients received PD-1/PD-L1 inhibitors alone (13.3%; 95%CI, 9.0%-19.3%) had lower objective response rate (ORR) compared to PD-1/PD-L1 inhibitors plus chemotherapy (62.5%; 95%CI, 54.4%-70.0%) or chemotherapy (41.6%; 95%CI, 36.8%-46.7%) while neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy (36.2%; 95%CI, 19.2%-57.6%) achieved elevated complete pathological complete response (pCR) eclipsing PD-1/PD-L1 inhibitors alone (10.6%; 95%CI, 6.5%-16.9%) and standard chemotherapy (7.5%; 95%CI, 5.7%-9.8%). Neoadjuvant chemotherapy (87.2%; 95%CI, 74.9%-94.0%) has numerically lower R0 resection rate in contrast to neoadjuvant PD-1/PD-L1 inhibitors alone (92.7%; 95%CI, 83.4%-97.0%) and PD-1/PD-L1 inhibitors plus chemotherapy (91.6%; 95%CI, 84.3%-95.7%). Subgroup analysis showed that increased proportion of stage III patients receiving neoadjuvant chemotherapy (p=0.025, Spearman r=0.761) may be correlated with lower R0 resection rate while no significant correlation was found in PD-1/PD-L1-based neoadjuvant treatment.

Conclusions

Compared to neoadjuvant chemotherapy, immunotherapy-based regimens provided superior pathological response along with higher complete resection rate especially for stage III disease. Immunotherapy combined chemotherapy as neoadjuvant setting may be a more preferable clinical option currently.

Legal entity responsible for the study

Wen-zhao Zhong.

Funding

National Natural Science Foundation.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

358P - Adjuvant tyrosine kinase inhibitors in non-squamous non-small cell lung cancer with EGFR driver mutations: An updated meta-analysis of randomized trials (ID 598)

Presentation Number
358P
Lecture Time
09:00 - 09:00
Speakers
  • Joanmarie C. Balolong-Garcia (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Current treatment guidelines state that resectable early stage NSCLC may be treated with adjuvant therapy in the form of chemotherapy and radiotherapy. For Nonsquamous Non-Small Cell Lung Cancer (NS NSCLC), Epidermal Growth Factor Receptor (EGFR) mutations may be present in up to 60% of cases. In the locally advanced and metastatic settings, EGFR tyrosine kinase inhibitors (TKI) have shown remarkable efficacy. With the basis of EGFR as a driver mutation for carcinogenesis, EGFR TKI treatment has been explored in several studies. However, the role of EGFR TKI in the adjuvant setting remains controversial due to lack of conclusive evidence. The latest treatment guidelines do not favor adjuvant EGFR TKI for EGFR-mutant resected early stage NS-NSCLC. Therefore, this meta-analysis evaluated existing randomized controlled trials (RCTs) for a more precise estimate of the efficacy of adjuvant EGFR TKI and associated lung cancer survival.

Methods

A systematic search of Pubmed, Embase, Cochrane, and clinical trials databases as well as hand search were utilized to identify RCTs investigating adjuvant EGFR TKI treatment in resected NS-NSCLC.

Results

Seven RCTs were included (N=2095), all contain disease free survival (DFS) data. Four trials gave EGFR TKI treatment for 24 months, while one trial provided EGFR TKI treatment for 36 months. Erlotinib, gefitinib, icotinib, and osimertinib were the EGFR TKI used in the RCTs. Treatment with adjuvant EGFR TKI showed statistically significant DFS benefit (HR 0.64, 95% CI[0.50-0.82)], P=0.0005) although with substantial heterogeneity (I2=98%, P<0.00001). This heterogeneity was attributed to trial phase and EGFR TKI generation used. Subgroup analyses were done for trial phase, treatment duration, disease stage, type of EGFR TKI, and toxicity. It was found that use of EGFR TKI gefinitib has statistically significant survival (DFS) advantage (HR 0.56, 95% CI(0.47-0.66), P<0.00001; I2=0%).

Conclusions

Results of this meta-analysis provide preliminary but strong evidence recommending EGFR TKI in the adjuvant setting among EGFR-mutant resected early NS NSCLC by improving DFS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

359P - The role of adjuvant targeted therapy for postoperative EGFR mutant non-small cell lung cancer: A network meta-analysis (ID 624)

Presentation Number
359P
Lecture Time
09:00 - 09:00
Speakers
  • Guang Ling Jie (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have shown promising efficacy in clinical trials for resected EGFR mutant NSCLC. However, it is still unclear which type of adjuvant regimens can provide best survival benefit among multiple therapeutic strategies. Herein, we performed a network meta-analysis to comprehensively compare the efficacy and safety of adjuvant treatments for resected EGFR mutant NSCLC.

Methods

Studies comparing two or more adjuvant treatments for resected EGFR mutant NSCLC were included. Study outcomes were DFS and OS with hazard ratio and adverse events with odds ratio. The primary endpoint was DFS. Registration number: PROSPERO (CRD42020184514).

Results

10 eligible trials involved 2707 patients and 6 treatments: 3 EGFR-TKIs (osimertinib, erlotinib, gefitinib), TKI following chemotherapy (CT+TKI), chemotherapy alone and placebo. Osimertinib showed the most favorable DFS, with significant superiority versus erlotinib (HR 0.4, 95% CI 0.24-0.66), gefitinib (0.42, 0.26-0.67), chemotherapy (0.23, 0.15-0.33) and placebo (0.17, 0.12- 0.24), but with no significant improvement versus CT +TKI (0.86, 0.42-1.74). CT +TKI provided the best OS benefit across assessable treatments (versus placebo, HR, 0.6 [0.11, 3.34]). OS data form osimertinib was not yet mature. Osimertinib had the fewest toxicity, whereas CT +TKI or chemotherapy alone caused most toxic effects. In subgroup analysis, EGFR-TKIs monotherapy provided more survival improvement for patients with exon 19 deletion than with L858R mutation (HR, 0.31 [0.13, 0.75] for exon 19 deletion, and 0.48 [0.35, 0.65] for L858R mutation, respectively).

Conclusions

These results showed that adjuvant EGFR-TKIs with or without chemotherapy can improve survival outcomes compared with placebo or adjuvant chemotherapy for resected EGFR-mutated NSCLC. Osimertinib provided the most DFS benefits and safety profile among the 6 treatments. Considering both efficacy and toxic effect, osimertinib is a promising agent in adjuvant setting for EGFR-mutant NSCLC, especially for those with exon 19 deletion.

Legal entity responsible for the study

Yi-Long Wu.

Funding

This project supported by the Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine (2017B0303141 20 to Y.L. WU), National Natural Science Foundation of China (81872510, 81673031 to W.Z. ZHONG).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

360P - Number of lymph nodes examined was not an independent risk factor for the survival of patients with stage IA1-2 lung adenocarcinoma undergoing sublobar resection (ID 473)

Presentation Number
360P
Lecture Time
09:00 - 09:00
Speakers
  • Zhenbin Qiu (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To explore the relationship between the number of reginal lymph nodes (LNs) examined and prognosis among patients with stage IA1-2 lung adenocarcinoma (LUAD) who underwent sublobar resection.

Methods

A total of 690 patients with stage IA1-2 LUAD patients from 2004-2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. of which 475 were grouped into 0<LNE (lymph nodes examined) ≤5 cohort and 215 were included in LNE>5 cohort for the cutoff value calculated through X-tile software. Two groups were compared in terms of overall survival (OS) and lung cancer-specific survival (LCSS). Propensity score matched (PSM) comparative analysis and Cox regression analysis were conducted.

Results

Before PSM, the patients with more LNs examined exhibited better OS and LCSS (Figure 1A&B). The median OS for 0< LNE≤5 cohort patients was 116.0 months, that for LNE >5 was 124.0 months (p=0.012; HR: 1.472, 95%CI: 1.107-1.959). The median LCSS for two cohorts were both not reached, respectively (p=0.044; HR: 1.498, 95%CI: 1.021-2.197). After PSM, 209 pairs of patients were matched and all variables were well balanced. And comparable OS and LCSS were observed between two matched cohorts (Figure 1C&D). The median OS for 0< LNE≤5 cohort patients was 122.0 months, that for LNE >5 was 124.0 months (p=0.28; HR: 1.187, 95%CI: 0.820-1.720). The median LCSS for two cohorts were both not reached, respectively (p=0.90; HR: 0.997, 95%CI: 0.588-1.692). Univariate and multivariate cox regression analysis revealed that the number of regional (LNs) examined was not an independent risk factors for OS or LCSS (Table; p=0.126, HR: 0.767, 95%CI: 0.479-0.919; p=0.237, HR: 0.773, 95%CI: 0.503-1.185).

Conclusions

The number of regional LNs examined did not correlate with the survival prognosis for stage IA1-2 lung adenocarcinoma patients who underwent sublobar resection.

Legal entity responsible for the study

The authors.

Funding

Key Lab System Project of Guangdong Science and Technology Department-Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120), Project of National Natural Science Foundation (Grant Nos. 81673031, 81872510), Research Fund from Guangzhou Science and Technology Bureau (Grant No. 201704020161), High-Level Hospital Construction Project (Grant No. DFJH201801), and Guangdong Provincial People’s Hospital Young Talent Project (Grant No. GDPPHYTP201902).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

361P - Radiomic model predicting radiological response after thoracic stereotactic body radiotherapy regardless of tumor histology and staging (ID 229)

Presentation Number
361P
Lecture Time
09:00 - 09:00
Speakers
  • Ben Man Fei Cheung (Hong Kong, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Thoracic stereotactic body radiotherapy (SBRT) is widely applied in both early and metastatic disease. Pathological CR rate after SBRT was quoted around 60%. Thus, it is important to predict responder and non-responder to SBRT. With advent of radiomics, textual features of tumor can be extracted from imaging. We propose a model to predict radiological response after SBRT based on tumor radiomics features regardless of histology and staging.

Methods

Patients receiving thoracic SBRT using active breathing control (ABC) were retrospectively recruited regardless of tumor histology/primary and staging. All patients received 50-54 Gy in 3-4 fractions equivalent to BED >100Gy. All patients had regular contrast CT Thorax per protocol and PET/CT if indicated. Tumor response was assessed by an independent senior radiologist based on RECIST criteria. Responders are defined as complete response (CR) or partial response (PR). Non-responders were defined as those with stable or progressive disease. Gross tumor volumes (GTV) were contoured on the initial planning CT. 110 radiomics features including voxel intensities, textual and gray level features were extracted using pyradiomics module. The features were then analyzed using in-house software. A model using support vector machine (SVM) was trained to predict response based solely on the extracted radiomics features. 10-fold cross validation was used to avoid overfitting. ROC curves were constructed to evaluate model performance.

Results

68 patients were recruited from 2008 to 2018. 54 patients had lung primaries while 14 patients had thoracic oligo-metastases. Secondaries include colorectal, head and neck squamous cell carcinoma and hepatocellular carcinoma. 85 tumors were analyzed, of which 31 tumors had CR and 11 tumors had PR. The radiomic model developed had an accuracy of 74.8%. The AUC for CR, PR and non-responder prediction was 0.865 (95% CI: 0.794 – 0.921), 0.946 (95% CI: 0.873 – 0.978) and 0.857 (95% CI: 0.789 – 0.915) respectively. Under the threshold, the sensitivity was 89% while the specificity was 68% for detecting non-responders.

Conclusions

Radiomic is a promising technique that can predict tumor response with good accuracy.

Legal entity responsible for the study

Department of Clinical Oncology, Queen Mary Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

362P - Integrative and comparative genomic analysis and immune microenvironment features of lung cancer patients with tuberculosis (ID 1045)

Presentation Number
362P
Lecture Time
09:00 - 09:00
Speakers
  • Xiaoling Xu (Hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

High prevalence of tuberculosis (TB). is observed in China, and one of the etiological factors for lung cancer is TB. Our study was aimed to compare the differences of the tumor microenvironment (TME) based on tumor PD-L1 expression and CD3+/ CD4+/CD8+ T cells infiltration in patients with non-small cell lung cancer (NSCLC) who have ever/current suffered from TB to those lung cancer patients without TB.

Methods

Tumor samples from 69 patients with lung cancer who have ever/current suffered from TB were retrospectively collected at Zhejiang Cancer Hospital and Hangzhou Red Cross Hospital. The 21 samples of control group (lung cancer patients who never suffered from TB) is collected in Zhejiang Cancer Hospital. Tumoral PD-L1 expression (N = 68) and CD3+/CD4+/CD8+ T cells infiltration (N = 58) was determined by immunohistochemistry (IHC), based on which TME was categorized into different subtype. Proportion of four TME subtypes was determined, and overall survival with PD-L1 expression and TME was analyzed. The whole exon sequencing was used to detect the different immune gene landscape between 40 lung cancer patients who have ever/current/never suffered from TB.

Results

Patients with TB had a decrease of infiltration of PD-L1 expression and CD8+ T cells into tumors. In addition, a different prognosis was observed in patients with active TB. The WES test showed a significant difference in TP53 mutation, tumor mutation burden, neoantigen and mutation signature in lung patients with or without TB. Lung patients with TB had unique driver genes such as C1QB, CDKN2A and signaling pathways. After analyzing in TIMER database, TP53,C1QB, CDKN2A are closely related to various immune cells in NSCLC.

Conclusions

NSCLC patients with TB exhibited lower PD-L1 and CD8+ expression level in TME and have different genomic landscape compare to lung cancer patients. Immunotherapy may have less effective in patients with active or latent TB and is prone to re-ignition of TB because of the reduced expression of PD-L1 and CD8+. Novel C1QB and CDKN2A targeted therapies may be the future direction of treatment for these patients with lung cancer and TB.

Legal entity responsible for the study

Zhejiang cancer hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

363P - Genetic predisposition for pre-invasive lung adenocarcinoma manifesting as ground-glass nodules with family history of lung cancer (ID 454)

Presentation Number
363P
Lecture Time
09:00 - 09:00
Speakers
  • Rui Fu (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lung cancer with family history have been increasing gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The genome predisposition of GGNs with lung cancer family history remains baffling.

Methods

This prospective study (NCT04220268) enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, which presenting as GGNs in computer tomography (CT) scans. We collected blood and tumor samples from 59 patients with GGNs and first-degree relative family history of lung cancer (FHLC) to investigated germline and somatic mutations by whole exome sequencing (WES). Pre-invasive neoplasia causal variants were detected by quality, classification, minor allele frequency (MAF), functional prediction, and family segregation filter. Validation was conducted in an external cohort of 669 healthy participants without cancer, and in 126 nonoverlapping susceptibility loci for lung carcinogenesis identified by recent genome-wide association studies (GWAS).

Results

Eighty-five single nucleotide variants (SNVs) and 11 frameshifts were detected, which were rare, predicted as damaging, and presented in more than two families. Fifteen of them had been reported that were associated with high risk of lung cancer or deleterious function. The MAF of them were lower than 0.01 in a local health Asian cohort and human exome databases. Three of them were validated in 126 susceptibility loci for lung carcinogenesis. The number of the rare, damaging and repeatedly germline mutations in non-smoking patients were significantly higher than those in smoking patients (2436 vs 593, p<0.05). The number of these germline mutation showed no significant difference between the patients with pure GGNs and mixed GGNs (1298 vs 1333, p>0.05).

Conclusions

Patients with GGNs and FHLC may have inheritable carcinogenesis mutations. These variants may potentially contribute to the risk of pulmonary pre-invasive adenocarcinoma susceptibility in Chinese population.

Legal entity responsible for the study

The authors.

Funding

Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine (Grant No. 2017B030314120), National Natural Science Foundation of China (Grant No. 81673031&No. 81872510), High-level Hospital Construction Project (DFJH201801), Guangdong Provincial People's Hospital Young Talent Project (No. GDPPHYTP201902).

Disclosure

R-R. Chen, Z-X. Tai, H-X. Lin: Full/Part-time employment: GenePlus-Beijing Institute, Beijing, China. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

364P - A deep learning model for the classification of lung cancer (ID 416)

Presentation Number
364P
Lecture Time
09:00 - 09:00
Speakers
  • Gouji Toyokawa (FUKUOKA, Fukuoka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lung cancer treatment gets on the stage of precision medicine. Histopathological classification of lung cancer is crucial in determining optimum treatment. Artificial intelligence (AI) models have been widely shown to be useful in pathological diagnosis and we previously established a reliable AI model to detect the presence of lung cancer on whole slide images (WSIs). However, AI models for the differentiation of major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC) and small-cell lung cancer (SCLC), are yet to be established.

Methods

We trained a convolution neural network (CNN) based on the EfficientNet-B1 architecture to classify ADC, SCC, SCLC, and non-neoplastic lesion from biopsy specimen WSIs (70, 23, 12 and 171 specimens with ADC, SCC, SCLC and non-neoplastic lesion, respectively) using a training dataset of 276 images of which 60 were reserved for validation. The WSIs were manually annotated by pathologists by drawing around the regions that contain each subtype. We used a transfer learning approach, in which the starting weights were obtained from a pre-trained model on ImageNet. The model was then trained on our dataset using a supervised learning approach. To classify a WSI, the model was applied in a sliding window fashion with an input tile size of 224x224 and a stride of 128 on a magnification of x10. The maximum probability was then used as a WSI diagnosis.

Results

We evaluated our model on a total of 533 WSIs that only had WSI diagnoses. The model achieved a Receiver Operator Curve Area Under the Curves of 0.888 (CI 0.872-0.9075), 0.8913 (CI 0.8596-0.9221), 0.9526 (CI 0.9276-0.9646) for ADC, SCC, and SCLC, respectively.

Conclusions

The obtained results on a large test set are a promising first step towards developing a model for the classification of lung cancer. Our model was only trained on a small dataset of 276 WSIs; however, we hope that the model would be further improved with the collection of additional annotated WSIs for training. Having a high performing model could help reduce the burden on pathologists and be useful for the decision of optimum treatment strategies, such as molecular-targeted therapy, immunotherapy and chemotherapy, according to the histological types of lung cancer.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

365P - Utilization of on-site pathology evaluation for lung cancer diagnosis in the Philippines’ National University Hospital (ID 723)

Presentation Number
365P
Lecture Time
09:00 - 09:00
Speakers
  • Rich Ericson King (Manila, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Access to biopsy services is a limiting factor to timely lung cancer diagnosis in many areas in the Philippines. On-site pathology evaluation allows for rapid diagnosis and helps ensure adequate specimen sampling. In our institution, its utilization and impact have not yet been evaluated.

Methods

We reviewed biopsy records of patients diagnosed with lung cancer in a tertiary teaching hospital in the Philippines from September 2017 to August 2019. For each procedure, we determined whether on-site pathology evaluation was performed. Furthermore, its association with the need for re-biopsy, time to cancer diagnosis, receipt of systemic treatment and time to treatment initiation was determined. We used the z test for two proportions to anlayze binary variables, and the Mann-Whitney U test for continuous variables.

Results

A total of 112 pathology reports on 88 patients were reviewed. On-site evaluation was performed in 25 (22.3%) procedures (frozen section in 15, adequacy evaluation in 10). A re-biopsy was recommended in 37 procedures (33.0%) due to inadequate yield, of which only 24 (64.9%) were pursued. Patients who did not undergo on-site evaluation had a longer median time to cancer diagnosis (34 vs. 17 days, p = 0.04) and were more likely to require a re-biopsy (41% vs. 12%, p = 0.01). They were also less likely to eventually undergo systemic treatment (22.8% vs. 53.3%, p = 0.02), while a trend for a longer median time to treatment initiation did not reach statistical significance (145 vs. 83 days, p = 0.14). Among procedures where on-site evaluation was performed, there were only three instances when a repeat biopsy was recommended. In one case, the specimen was judged to be inadequate, but this was not followed by sampling of more tissue. In the other two cases, the specimen was deemed adequate but turned out to be insufficient for immunohistochemical evaluation.

Conclusions

On-site pathologic evaluation was associated with an earlier lung cancer diagnosis, a reduced need for a repeat biopsy, and a higher proportion of patients eventually receiving treatment. Efforts should be undertaken to increase the utilization of this service in order to optimize the quality of care for these patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R.E. King: Research grant/Funding (institution), Recipient of Pfizer Global Medical Grant: Pfizer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

Thoracic tumours, locally advanced (ID 1158)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

368P - Real-world characteristics, treatment, and outcomes of stage III non-small cell lung cancer in Japan: SOLUTION study (ID 212)

Presentation Number
368P
Lecture Time
09:00 - 09:00
Speakers
  • Haruyasu Murakami (Shizuoka, Shizuoka, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous population ranging from apparently resectable tumors to inoperable disease. Patients diagnosed with stage III NSCLC can be treated with surgery, chemoradiotherapy, radiotherapy, and chemotherapy, depending on clinical decision by disease condition such as tumor volume, presence and number of lymph node metastasis, and patient’s background. This study aims to clarify the treatment reality in Japanese patients with stage III NSCLC.

Methods

A retrospective observational study was conducted in 11 institutions in Japan, and patients diagnosed as clinical stage III NSCLC during January 2013 to December 2014 were included. We evaluated the patient characteristics, details of treatments, and efficacy and safety outcomes per each treatment choice.

Results

In total, 790 patients were enrolled in this study, of whom 744 patients were full analysis set (FAS). Patient characteristics at diagnosis were as follows: Median age was 68 years old. Number of resectable and unresectable at diagnosis were 186 (25%) and 558 (75%), respectively. Number of stage IIIA and IIIB were 438 (59%) and 306 (41%). Number of patients per treatment modality was as follows: surgery (including both with and without perioperative treatment), 149 (20%); chemoradiotherapy, 343 (46%); chemotherapy alone, 165 (22%); and radiotherapy alone, 87 (12%). The proportion of stage IIIA was 96% in the surgical group and 39%-61% in the other groups. The median overall survival (mOS) of FAS was 25 months, and the 5-year survival rate was 28%. The mOS of surgery, chemoradiotherapy, chemotherapy, and radiotherapy were 43, 30, 17, and 14 months, and the 5-year survival rates were 44%, 33%, 14%, and 6%, respectively. The incidence of pneumonitis and radiation-pneumonitis in patients treated with chemoradiotherapy was 37% and in radiotherapy was 16%.

Conclusions

To our knowledge, this is the first study reporting the treatment reality in patients diagnosed with stage III NSCLC in Japan. Our study revealed the proportion of initial treatment in the real-world practice accompanied with the patient characteristics, prognosis, and safety focusing on radiation-related adverse events.

Clinical trial identification

UMIN000031385.

Legal entity responsible for the study

AstraZeneca K.K.

Funding

AstraZeneca K.K.

Disclosure

H. Murakami: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self): Ono; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): IQVIA. H. Harada: Honoraria (self): AstraZeneca; Honoraria (self): Brainlab; Honoraria (self): Taiho; Honoraria (self): Nippon Chemiphar ; Honoraria (self): Merck Biopharma; Honoraria (self): Chugai; Honoraria (self): Novartis. S. Atagi: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self): Hisamitsu; Honoraria (self): Kyowa Kirin; Research grant/Funding (institution): F. Hoffmann-La Roche. T. Tokito: Honoraria (self): AstraZeneca; Honoraria (self): Chugai; Honoraria (self): Boehringer Ingelheim. S. Oizumi: Honoraria (self), Research grant/Funding (institution): AstraZeneca. T. Kozuki: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self): Ono; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Nippon Kayaku; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Kyowa Kirin; Honoraria (self): Pfizer; Research grant/Funding (institution): Merck Biopharma. M. Seike: Honoraria (self): AstraZeneka; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Boehringer Ingelheim. M. Jinushi: Full/Part-time employment: AstraZeneca. H. Horinouchi: Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Genomic Health; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Ono. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

369P - The surgical perspective in neoadjuvant immunotherapy for resectable non-small cell lung cancer (ID 375)

Presentation Number
369P
Lecture Time
09:00 - 09:00
Speakers
  • Long Jiang (Hangzhou, Guangdong, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

More recently, the novel conception of neoadjuvant immunotherapy has generated interest among surgeons worldwide, especially the lack of experience involving surgical treatment for the neoadjuvant immunotherapy population. To address this, the current study was conducted to report the analysis of surgical perspective outcome data after neoadjuvant immunotherapy followed by surgery for resectable non-small-cell lung cancer (NSCLC).

Methods

The current retrospective study was conducted at Shanghai Chest Hospital, an ultra-high-volume tertiary thoracic surgery center in Shanghai, China. Patients with NSCLC, who underwent neoadjuvant immunotherapy or chemo-immunotherapy were retrospectively collected between September 2018 and April 2020. Demographic data, pathologic and clinical features, therapeutic regimens, and outcome data of all individuals were collected by retrospective chart review. Operative details, information of neoadjuvant therapy, were also abstracted.

Results

Of the 14901 patients underwent lung resection in our institute during the study period, 31 patients received neoadjuvant immunotherapy or chemo-immunotherapy for at least 2 courses were included in the study. The patients’ median age was 61 years. 29 of the patients were males while 2 were females. Patients received a median of 3 doses before resection. The median duration from final treatment to surgery was 34 days. After neoadjuvant treatment, post-treatment computed tomography scan showed that 24 patients had partial response. 12 of 31 patients had a major pathologic response, 15 pathologic downstaging. Three patients had no residual viable tumor. A positive surgical margin was identified in 7 cases. One or more postoperative complications occurred in 18 of all 31 patients. 26 of these 31 patients underwent next-generation sequencing (NGS) before surgery in total. Among them, 2 patients (7.7%) were detected STK11 mutations. None of these 2 individuals had an MPR by final pathological examination.

Conclusions

Pulmonary resection after neoadjuvant immunotherapy or chemo-immunotherapy for resectable NSCLC appears to be safe with low operative mortality and morbidity rate in the current population.

Legal entity responsible for the study

The authors.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81702251 and 81972176), the Science Foundation of Shanghai (No.18ZR1435100) and Shanghai Hospital Development Center (SHDC12016113).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

371P - Real-world insights into treatment patterns and outcomes in stage III non-small cell lung cancer (NSCLC): KINDLE study India analysis (ID 712)

Presentation Number
371P
Lecture Time
09:00 - 09:00
Speakers
  • Kumar Prabhash (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Heterogeneous nature and poor prognosis of stage III NSCLC, accounting for ≈29% of NSCLC burden, cause substantial management challenges in India. We present the results of Indian cohort from the real-world, multicountry, observational KINDLE study that explored treatment patterns and associated outcomes in the pre-immuno-oncology era.

Methods

Retrospective data from 15 sites in India were analyzed for stage III NSCLC patients diagnosed between 01Jan2013 and 31Dec2017 with at least 9 months (m) of documented follow-up. Descriptive analyses for demographics, clinical characteristics, and treatment modalities, and inferential statistics to correlate treatment with progression-free survival (PFS) and overall survival (OS) were conducted.

Results

Data for 494 patients: median age 60.0 years (range 25-84), 83.4% men, 58.7% current/former smokers, and 48.2% and 51.8% with stage IIIA and IIIB NSCLC (AJCC 7th ed.), respectively; 84.9% had ECOG performance score of 0/1 at diagnosis. Squamous cell and adenocarcinoma represented 48.5% and 44.6%, respectively; 15.4% had EGFR mutations. Of the 18 first-line treatment modalities, the most frequent were concurrent chemoradiotherapy (cCRT) (29.5%), sequential CRT (13.6%), chemotherapy (CT) alone (13.3%), and radiotherapy alone (12.7%). Overall median PFS was 16.4m, 95% confidence interval (CI) 14.36-19.38 (stage IIIA: 19.4m, 95% CI 15.08-25.95; IIIB: 15.4m, 95%CI 12.45-19.78). Overall median OS was 66m, 95% CI 49.81-noncalculable (NC); (stage IIIA: NC, 95% CI 52.14-NC; IIIB 66.0m, 95% CI 36.04-NC). In stage IIIA patients, cCRT was associated with longer OS than CT alone (64.1m vs. 30.0m, p=0.0493). Among stage IIIB patients, cCRT was associated with significantly higher OS than CT alone (66.0m vs. 22.6m, p=0.0226).

Conclusions

The India data reveal varied treatment modalities in stage III NSCLC. Overall median PFS and OS were better for India (16.4m and 66m) than in the global cohort (12.5m and 34.9m). cCRT was associated with improved survival in both stage IIIA and IIIB. Improved access to newer medicines and quality care will be key to further enhance patient outcomes.

Clinical trial identification

Protocol - D133HR00004 NCT03725475.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

A. Kumar, R. Huggenberger, S. Robb: Full/Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

373P - Chromatin accessibility reveals potential prognostic value of the peak set associated with smoking history in patients with lung adenocarcinoma (ID 894)

Presentation Number
373P
Lecture Time
09:00 - 09:00
Speakers
  • Jianlian Deng (Shenzhen, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Considerable differences in molecular characteristics have been defined between non-smokers and smokers in patients with lung adenocarcinoma (LUAD). However, study of open chromatin patterns associated with LUAD progression caused by smoking is still lacking.

Methods

Here, we firstly constructed a novel network based on correlations between each ATAC-seq peak from TCGA data using our previously developed algorithm. Subsequently, principal component analysis was performed on LUAD samples with retained peaks filtered by the correlation network. Prognostic value of the significant ATAC-seq peak set with overall survival in these smoking related LUAD patients was assessed. Then, pathway analysis of the peak-related genes was conducted for potential pathways identification.

Results

We identified a set of peaks with significant correlation that clearly differentiated long-term smokers from those with short-term smoking history in LUAD patients and also significantly associated with overall survival of these patients. The gene set that were demonstrated to be related to those peaks, such as B3GNT3, ACTN4 and CLDN3, are strongly associated with LUAD development, which is consistent with the important roles for the associated pathways in LUAD oncogenesis induced by smoking, including glycosphingolipid biosynthesis and tight junction pathways.

Conclusions

Our study may provide valuable insights on exploration of ATAC-seq peaks and on smoking-related LUAD carcinogenesis from a perspective of open chromatin changes.

Legal entity responsible for the study

BGI-Shenzhen, Shenzhen 518083, China.

Funding

Science, Technology, and Innovation Commission of Shenzhen Municipality.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

374TiP - LAURA: Osimertinib maintenance following definitive chemoradiation therapy (CRT) in patients (pts) with unresectable stage III epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC) (ID 533)

Presentation Number
374TiP
Lecture Time
09:00 - 09:00
Speakers
  • Shun Lu (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Platinum-based CRT followed by durvalumab consolidation (PACIFIC study regimen) is standard of care for pts with unresectable Stage III NSCLC, without progression after platinum-based CRT. In PACIFIC, only 6% of pts had EGFRm NSCLC. Osimertinib is a 3rd-generation, CNS-active, oral, irreversible EGFR tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations. FLAURA data (median OS: HR 0.80; 95.05% CI 0.64, 1.00; P=0.046) indicate osimertinib could provide benefit to pts with unresectable Stage III NSCLC. LAURA (NCT03521154) will assess the efficacy and safety of osimertinib as maintenance therapy in pts with locally advanced, unresectable, EGFRm, Stage III NSCLC without disease progression during/following definitive platinum-based CRT. Previously presented: WCLC, Shun L et al. 2018 J Thorac Oncol;13(10 suppl):S497; we report protocol updates (Feb 2020).

Trial design

In this Ph III, double blind, placebo-controlled trial, pts will be randomized (2:1) to osimertinib 80 mg/day or placebo, until objective radiological disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, confirmed by blinded independent central review (BICR). Key inclusion criteria: ≥18 years (≥20 Japan); locally advanced unresectable Stage III NSCLC; central/local confirmation of Ex19del/L858R; WHO PS 0–1; ≥2 cycles of concurrent/sequential platinum-based CRT; no investigator-assessed (IA) progression; creatinine <1.5x ULN and creatinine clearance ≥30 mL/min. Primary objective: to assess the efficacy of osimertinib by BICR progression-free survival (PFS). Secondary objectives: PFS by mutation status, CNS PFS, OS and safety. Pts with BICR-confirmed disease progression (IA-confirmed if after PFS analysis) may be un-blinded to receive open-label osimertinib; all will have post-progression follow-up. Serious adverse events (SAEs) and AEs of special interest will be collected throughout the study and survival follow-up. First pt enrolled July 2018; results expected late 2022.

Clinical trial identification

NCT03521154.

Editorial acknowledgement

The authors would like to thank Laura Crocker, BMedSci of Ashfield Healthcare Communications, part of UDG Healthcare plc, who provided medical writing support funded by AstraZeneca, Cambridge, UK, the manufacturer of osimertinib, in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S. Lu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Hutchison MediPharma; Advisory/Consultancy: Simcere; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Advisory/Consultancy: GenomiCare; Research grant/Funding (self): Hutchison; Research grant/Funding (self): Bristol Myers Squibb; Research grant/Funding (self): Heng Rui; Speaker Bureau/Expert testimony: Hansoh. T. Kato: Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Biopharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ono; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Nippon Kayaku; Advisory/Consultancy: Nitto Denko; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Chugai; Speaker Bureau/Expert testimony: Taiho, Daiichi-Sankyo, F. Hoffmann-La Roche, Shionogi, Sumitomo Dainippon; Licensing/Royalties: Astellas, Kyorin, Kyowa-Kirin, Regeneron; Research grant/Funding (self), Personal fees: AstraZeneca. M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Astellas; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Roche. L. Zeng: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. T. van der Gronde, M. Saggese: Full/Part-time employment: AstraZeneca. S. Ramalingam: Advisory/Consultancy, Research grant/Funding (self): Amgen; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): Tesaro; Advisory/Consultancy, Research grant/Funding (self): Takeda; Research grant/Funding (self): Advaxis; Research grant/Funding (self): Genmab. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

YO19 - Recurrent primary mediastinal seminoma with sarcomatous transformation. (ID 831)

Presentation Number
YO19
Lecture Time
09:00 - 09:00
Speakers
  • Sopiko Gogia (Tbilisi, Georgia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Case summary

Introduction

Extragonadal germ cell tumors are rare and comprise a heterogeneous group of neoplasm1. Somatic transformation occurs in 2% of GCT and it is even rarer in extragonadal sites2. The exact pathogenic mechanism is unknown. The prognosis is unfavorable because cisplatin-based chemotherapy is not effective2. Surgical resection is the mainstay of the treatment.

Case report

A 26- year-old male presented with cough, shortness of breath, fever. Chest CT revealed a mass 10 cm in size at the level of 3rd -8th ribs. Right-sided pleural effusion was noted. Histologic evaluation revealed pure seminoma. Serum markers were elevated. The patient received 4 cycles of chemotherapy with BEP regimen. Serum markers decreased to baseline.PET/CT done after 4 months since diagnosis showed a reduction in the size of the tumor. Gross tumor volume was irradiated. Upon restaging, PET /CT showed a complete metabolic response. Chest CT done 3 years thereafter showed an anterior mediastinal mass 52 mm in size. PET/CT confirmed the presence of a mass lesion consistent with the recurrence of the primary disease. Chemotherapy was initiated with a VIP regimen. The mass decreased in size. Radical resection of the tumor was done. The tissue was positive for vimentin and negative for PanCK, EMA, S-100, desmin, C-kit, PLAP, HCG, Ki 67 -50%. The diagnosis of pleomorphic sarcoma was made.

Follow up CT after 4 months showed recurrence. The decision was made to initiate chemotherapy with docetaxel/gemcitabine.

Conclusion

The occurrence of somatic type malignancy in germ cell tumors is rare. The reported case is unique because of the location and histology of the primary tumor. Our case confirms that transformed tumors do not respond to GTM-based chemotherapy regimens and surgery is the mainstay of the therapy.

References

1. Dieckmann KP, Anheuser P, Gehrckens R, Wilczak W, Sauter G, Höflmayer D. Pure Testicular Seminoma Relapsing Late with Somatic Type Malignancy. Case Rep Oncol Med. 2017;2017:2457023. doi:10.1155/2017/2457023

2. O. El Mesbahi, M.-J. Terrier-Lacombe, C. Rebischung, C. Theodore, D. Vanel, and K. Fizazi, “Chemotherapy in patients with teratoma with malignant transformation,” EuropeanUrology,vol.51,no.5,pp.1306–1312,2007

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e-Poster Display Session (ID 87) Poster Display

Thoracic tumours, metastatic (ID 1159)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

384P - BLU-945, a highly potent and selective 4th generation EGFR TKI for the treatment of EGFR T790M/C797S resistant NSCLC (ID 689)

Presentation Number
384P
Lecture Time
09:00 - 09:00
Speakers
  • Stefanie S. Schalm (Cambridge, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR-mutant (L858R and ex19del) driven non-small-cell lung cancer (NSCLC). T790M is the most prevalent acquired EGFR resistance mutation to treatment with 1st and 2nd generation TKIs. 3rd generation TKIs, such as osimertinib, were developed to treat patients with tumors driven by this mutation. The C797S mutation is the most significant on-target resistance mechanism to osimertinib, leading to EGFR T790M/C797S double-resistant mutants. There are currently no approved targeted therapies for NSCLC patients with T790M/C797S mutations. BLU-945 is designed to target and selectively inhibit the EGFR T790M/C797S and T790M resistant mutations.

Methods

BLU-945 activity on EGFR mutants and EGFR wild-type (WT) was tested in biochemical assays and cellular phosphorylation specific EGFR AlphaLisa assays. The in vivo anti-tumor activity of BLU-945 was evaluated in an NCI-H1975 cell line-derived tumor xenograft (CDX) model, as well as in osimertinib-resistant CDX- and patient-derived xenograft (PDX) models of NSCLC.

Results

BLU-945 inhibits EGFRex19del/T790M/C797S, EGFRL858R/T790M/C797S, EGFRex19del/T790M, and EGFRL858R/T790M mutants with sub-nanomolar IC50 values in an enzyme assay with a >1000-fold window over EGFRWT enzyme activity. BLU-945 achieves potent EGFR pathway inhibition in NCI-H1975 EGFRL858R/T790M, Ba/F3 EGFRL858R/T790M/C797S, and Ba/F3 EGFRex19del/T790M/C797S cell lines and a large window relative to EGFRWT inhibition. Oral administration of BLU-945 to tumor-bearing mice demonstrated potent EGFR pathway inhibition and anti-tumor activity at well-tolerated doses in the subcutaneous NCI-H1975 CDX model, and osimertinib-resistant CDX and PDX models, as well as in the intracranial luc-H1975 model of NSCLC.

Conclusions

BLU-945 is a potent, selective, and orally available EGFR inhibitor that shows robust anti-tumor activity in osimertinib-resistant EGFR xenograft models. Because of its pharmacological activity and selectivity for mutant EGFR, BLU-945 has the potential to demonstrate activity in osimertinib-resistant EGFR-mutant NSCLC.

Editorial acknowledgement

Medical writing support was provided by Cristina Tomas, PhD, and editorial support by Sinead Stewart, both of Paragon, Knutsford, UK, supported by Blueprint Medicines Corporation.

Legal entity responsible for the study

Blueprint Medicines Corporation.

Funding

Blueprint Medicines Corporation.

Disclosure

S.S. Schalm, T. Dineen, J. Hsieh, R. Woessner, Z. Zhang, M. Eno, D. Wilson, J. Campbell, C. de Savi, F. Stevison, C. Utt, M. Dorsch, K. Hoeflich: Shareholder/Stockholder/Stock options, Full/Part-time employment: Blueprint Medicines Corporation. K. Wilson, B. Williams, T. Guzi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Formerly of Blueprint Medicines Corporation. B.C. Cho: Advisory/Consultancy, Research grant/Funding (self): Novartis; Research grant/Funding (self): Bayer; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): MOGAM Institute; Research grant/Funding (self): Dong-A ST; Research grant/Funding (self): Champions Oncology; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Research grant/Funding (self): Yuhan; Advisory/Consultancy, Research grant/Funding (self): Ono; Research grant/Funding (self): Dizal Pharma; Advisory/Consultancy, Research grant/Funding (self): MSD; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Medpacto; Research grant/Funding (self): GIInnovation; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy, Research grant/Funding (self): Blueprint Medicines Corporation; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

385P - Patient reported outcomes (PROs) analysis for patients with ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) receiving entrectinib in the global phase II STARTRK-2 study (ID 335)

Presentation Number
385P
Lecture Time
09:00 - 09:00
Speakers
  • Fabrice Barlesi (Villejuif, CEDEX 20, France)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In the ongoing STARTRK-2 study (NCT02568267), entrectinib demonstrated a favourable efficacy and safety profile in patients with locally advanced/metastatic ROS1+ NSCLC. We present the results of a pre-specified PRO analysis in an updated dataset with longer follow-up.

Methods

The European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30), and lung cancer module (QLQ-LC13) were completed prior to entrectinib dosing on Day 1 of every treatment cycle, and at end of treatment. The safety analysis set (SAS; patients received ≥1 entrectinib dose) was used to assess treatment-related symptoms. The efficacy analysis set (EAS; SAS patients with measurable baseline disease) was used to assess tumor-related symptoms, functioning, and global health status (GHS).

Results

At the data cut-off (1 May 2019), the SAS and EAS included 180 and 145 patients, respectively. GHS and functioning scores were maintained or improved during treatment, with the exception of cognitive functioning (Table). Tumor-related symptoms remained stable or trended towards improvement over time. For treatment-related symptoms, insomnia and appetite loss improved, while constipation and diarrhea worsened.

Conclusions

Among ROS1+ NSCLC patients, the treatment burden associated with entrectinib was minimal. There was a trend towards improved physical and role functioning, GHS, and tumor-related symptoms (particularly cough) while receiving entrectinib

ROS1+ NSCLC
Mean baseline score Change at Cycle 18 Day 1†
QLQ-C30* (EAS)
GHS 56.04 4.05
Functioning
Physical 71.51 5.72
Role 62.44 3.60
Cognitive 82.75 -7.66
QLQ-LC13* (EAS)
Tumor-related symptoms
Cough 38.57 -24.07
Chest pain 18.57 -3.70
Dyspnea 32.30 -6.17
Peripheral neuropathy 14.05 0.00
Dysphagia 7.14 5.56
QLQ-C30* (SAS)
Treatment-related symptoms
Insomnia 32.01 -14.97
Appetite loss 28.03 -15.65
Nausea and vomiting 10.80 -6.80
Constipation 16.67 11.56
Diarrhea 7.39 10.20

*Clinically meaningful change from baseline: >10 points. Last cycle with ≥25% patient enrollment. Occupational/social. Higher scores indicate improvement for GHS and functioning, worsening for symptom scales.

.

Clinical trial identification

STARTRK-2 study: NCT02568267.

Editorial acknowledgement

Alix Biancardi, Gardiner-Caldwell Communications.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

F. Barlesi: Advisory/Consultancy, Personal finance interests: AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F Hoffmann-La Roche, Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda; Research grant/Funding (institution): AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F Hoffmann-La Roche, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, Merck Sharp and Dohme, Pierre Fabre, Pfizer; Research grant/Funding (institution): Sanofi-Aventis, Takeda. J. Wolf: Advisory/Consultancy: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Research grant/Funding (institution): MSD, BMS, Janssen Pharmaceutica, Novartis, Pfizer. M-J. Ahn: Honoraria (institution): AstraZeneca, Lilly, Takeda, Roche, MSD; Advisory/Consultancy: AstraZeneca, Lilly, Takeda, Roche, MSD, Merck, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, and Alpha Pharmaceutical, Progeneer. R.C. Doebele: Advisory/Consultancy: Ignyta, Genentech/Roche, Loxo Oncology, Bayer, Eli Lilly, AstraZeneca, Pfizer, Blueprint Medicines, Anchiano, Rain Therapeutics; Research grant/Funding (institution): Ignyta, Loxo, Mirati, Pfizer, Eli Lilly, Strategia; Travel/Accommodation/Expenses: Ignyta, Genentech/Roche, Eli Lilly, Pfizer, Blueprint Medicines, Rain Therapeutics; Shareholder/Stockholder/Stock options: Rain Therapeutics; Licensing/Royalties: Ignyta, Loxo, Abbott Molecular, Genentech/Roche, Chugai, Foundation Medicine, Black Diamond, Rain Therapeutics, Voronoi, Pearl River, Ariad (patent and biologic material licensing fees). L. Paz-Ares: Advisory/Consultancy: Genentech/Roche, Loxo Oncology, Bayer, Eli Lilly, AstraZeneca, Pfizer, Bayer, Merck Sharp & Dohme, Novartis, Amgen, Pharmamar, Boehringer Ingelheim, Celgene, Servier, Sysmex, Incyte, Ipsen, Adacap, Sanofi, Blueprint Medicines; Research grant/Funding (institution): BMS, AstraZeneca, Merck Sharp & Dohme; Shareholder/Stockholder/Stock options: Altum Sequencing; Officer/Board of Directors: Genomica, Altum Sequencing. C. Rolfo: Advisory/Consultancy: Mylan, Oncompass, Archer, Inivata, MD Serono; Leadership role: IASLC Educational Committee Member and LATAM (IASLC) co-chair, ESO Scientific Committee Board, ISLB Vice president and Educational Chair, Educational Chair OLA; Research grant/Funding (institution): Biomarkers, Guardant Health (Research collaboration) Lung Cancer Research Foundation-Pfizer Grant, American Cancer Society grant, PY30 NIH grant. S. Siena: Advisory/Consultancy: Amgen, Payer, CheckMab, Celgene, Daiichi Sankyo, Incyte, Merck, Novartis, Roche, Seattle Genetics. T. Seto: Honoraria (institution): Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical; Research grant/Funding (institution): AbbVie, AstraZeneca, Bayer Yakuhin, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, Loxo Oncology, Merck Serono, MSD, Nippon, Boehringer Ingelheim, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical; Full/Part-time employment: Precision Medicine Asia; Honoraria (institution): Thermo Fisher Scientific. Y. Ohe: Honoraria (institution): AstraZeneca, Chugai, Eli Lilly, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin; Advisory/Consultancy: AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Research grant/Funding (institution): AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho, Novartis, Kissei, Ignyta, Takeda, Kissei, Daiichi-Sankyo, Janssen, LOXO. S.H.I. Ou: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer, Roche/Genentech, AstraZeneca, Takeda/ARIAD, Daiichi Sankyo; Research grant/Funding (institution): Pfizer, Roche/Genentech, AstraZeneca, Takeda/ARIAD, Daiichi Sankyo, Janssen, Mirati, Revolution Medicine, Lilly/Loxo Oncology, BluePrint Medicine; Shareholder/Stockholder/Stock options: Turning Point Therapeutics. M.G. Krebs: Honoraria (institution): Roche; Advisory/Consultancy: Roche, Janssen, Octimet, Achilles Therapeutics; Speaker Bureau/Expert testimony: Roche; Research grant/Funding (institution): AstraZeneca, Bayer, BerGenBio, Blueprint, BMS, Carrick, CellCentric, Chugai, Debiopharm, Genmab, Immutep, Incyte, Janssen, Kymab, Lilly, MedImmune, Merck, MSD, Novartis, Octimet, Roche, Sierra, StarPharma, Taiho, Turning Point Therapeutics; Travel/Accommodation/Expenses: AstraZeneca, BerGenBio; Research grant/Funding (self): Roche, BerGenBio. A. Kapre: Full/Part-time employment: Genentech/Roche. E. Piault-Louis: Full/Part-time employment: Genentech/Roche. S. McCallum: Full/Part-time employment: Genentech/Roche. S. Osborne, A. Aziez: Full/Part-time employment: Roche. A. Drilon: Honoraria (institution): Ignyta/Roche/Genentech, Loxo/Bayer/Lily, TP Therapeutics, AstraZeneca, Pfizer, Blueprint, Takeda/Ariad/Millennium, Helsinn, BeiGene, BerGenBio, Hengrui, Exelixis, Tyra, Verastem, MORE Health, AbbVie, 14ner/Elevation Oncology, Axis, Peerview Institute; Licensing/Royalties: Wolters Kluwer; Research grant/Funding (institution): Foundation Medicine, Pfizer, Exelixis, Taiho, Teva, GlaxoSmithKline, Pharmamar; Honoraria (institution): OncLive, Paradigm Medical Communications, Remedica Ltd., ArcherDX, Foundation Medicine, PeerVoice, Research to Practice, Medscape, WebMD.

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e-Poster Display Session (ID 87) Poster Display

386P - A single-arm phase Ib study of autologous cytokine-induced killer (CIK) cell immunotherapy in combination with sintilimab plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) (ID 448)

Presentation Number
386P
Lecture Time
09:00 - 09:00
Speakers
  • LI Zhou (Tianjin, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immune checkpoint inhibitors plus chemotherapy has demonstrated significant survival benefits for advanced non-small-cell lung cancer (NSCLC) patients without targetable mutations. Autologous cytokine-induced killer (CIK) cell therapy can restore the antitumor immunity to improve the patient outcomes. Therefore, a single-center, open-label, phase Ib trial was conducted to explore the efficacy and safety of autologous CIK cell therapy combined with sintilimab (anti-PD-1) plus chemotherapy as 1L treatment in advanced NSCLC patients (NCT03987867).

Methods

Systemic therapy naïve patients with stage IIIB-IV NSCLC would receive platinum-based doublet chemotherapy, sintilimab (200mg, d1), and intravenous autologous CIK cells (1010, d14) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoints were safetyand the objective response rate (ORR) assessed per RECIST v1.1.Secondary endpoints were progression-free survival (PFS) and overall survival (OS).

Results

From May 2019 to Jun 2020, 16 pts aged 46-72 years (median age 62 years) were enrolled. The squamous/non-squamous ratio was 44%/56%. 14 (87.5%) were men, 15(93.7%) were ECOG PS=0-1, 3 (18.75%) had liver metastases, and 2 (12.5%) had brain metastases. Among 13 evaluable pts, the ORR and DCR were 84.6% and 100%, respectively. Among the 11 PR assessed by RECIST, CR was demonstrated in 3 (23.1%) by PET-CT. At the time of data cutoff, the median DOR was not reached (range 2.43m-NA), and the median PFS and OS were not mature (median follow-up time 5.65m, range 0.63-13.3).Adverse events (AEs) occurred in 15 (93.75%), including 4 Grade≥3 AEs events (25%). The most common AEs were nausea (12, 75%), anemia (11, 68.75%), and leukopenia (10, 62.5%).Immune-related AEs were cardiomyopathy (1, 6.25%) and pneumonia (3, 18.75%),1 pts had immune-related grade 5 pneumonia.

Conclusions

Autologous CIK cell therapy in combination with sintilimab plus chemotherapy were well tolerated and showed encouraging efficacy. Further studies are warranted to confirm these preliminary results.

Clinical trial identification

NCT03987867.

Legal entity responsible for the study

The authors.

Funding

The National Key Technologies R&D Program of China grant Awards No. 2018YFC1313400 (to Jianchuan Xia).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

387P - Phase Ib study of savolitinib ± osimertinib in Japanese patients (pts) with advanced solid malignancies & EGFRm NSCLC: TATTON part C (ID 530)

Presentation Number
387P
Lecture Time
09:00 - 09:00
Speakers
  • Tomonori Hirashima (Habikino, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Preliminary data suggest that combining savolitinib (AZD6094, HMPL-504, volitinib), a potent and highly selective MET-tyrosine kinase inhibitor (TKI), with osimertinib, a 3rd generation, irreversible, oral epidermal growth factor receptor (EGFR) TKI that potently and selectively inhibits both EGFR mutations (EGFRm) and EGFR T790M, may overcome MET-driven resistance to EGFR-TKIs. The maximum tolerated dose (MTD) of savolitinib regimens in Japanese pts was evaluated in Part C of the phase Ib, multi-arm, open-label, multicenter TATTON study (NCT02143466).

Methods

Two dose-finding cohorts of pts (≥20 years) received savolitinib monotherapy (pts with advanced solid malignancies; savolitinib 400/600 mg once daily [QD]) or savolitinib/osimertinib combination therapy (pts with EGFRm non-small cell lung cancer [NSCLC] who progressed on 1st/2nd-generation EGFR-TKI; osimertinib 80 mg + savolitinib 300/400/600 mg QD). Primary endpoints were safety/tolerability and to define the combination dose(s) for further clinical evaluation. Secondary endpoints for combination included evaluation of tumor response.

Results

Seventeen pts received savolitinib monotherapy (400 mg, n=7/17; 600 mg, n=10/17) and 12 received the combination (savolitinib dose 300 mg, n=2/12; 400 mg, n=6/12; 600 mg, n=4/12). Serious adverse events (AE) were reported in 5/17 and 3/12 of pts, and AEs possibly causally related to savolitinib leading to its discontinuation were reported in 3/17 and 6/12 respectively. Dose-limiting toxicities data are included in the table, all except one were reversible. Pts receiving the combination (across doses) had an objective response rate of 42% (95% confidence interval 15.2, 72.3).

Conclusions

The MTD of savolitinib was 400 mg QD in both monotherapy and combination cohorts. Preliminary data demonstrate an acceptable safety profile for savolitinib and suggest antitumor activity in combination with osimertinib in Japanese pts with EGFRm NSCLC

Dose Evaluable patients with DLT DLT*
Monotherapy
Savolitinib 400 mg 0/6
Savolitinib 600 mg 3/9 Grade 3 ALT increase, Grade 3 AST increase
Grade 4 ALT increase, Grade 4 AST increase
Grade 4 drug-induced liver injury#
Combination therapy
Savolitinib 300 mg + Osimertinib 80 mg 0/2
Savolitinib 400 mg + Osimertinib 80 mg 1/6 Grade 2 fatigue, Grade 2 nausea, Grade 2 myalgia
Savolitinib 600 mg + Osimertinib 80 mg 3/4 Grade 2 pyrexia
Grade 3 skin reaction
Grade 3 anaphylactic shock

*n=1 for all events #Not recovered/not resolved Guidelines are now in place regarding hypersensitivity-related AEs ALT, alanine aminotransferase; AST, aspartate aminotransferase; DLT, Dose-limiting toxicity

.

Clinical trial identification

NCT02143466.

Editorial acknowledgement

Bernadette Tynan, MSc, of Ashfield Healthcare Communications, Macclesfield, UK, for medical writing support that was funded by AstraZeneca, Cambridge, UK, in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

T. Hirashima: Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical Co. Ltd; Honoraria (self), Research grant/Funding (self): Lilly Japan Co. Ltd.; Honoraria (self), Research grant/Funding (self): AstraZeneca Co. Ltd.; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant/Funding (self): MSD Oncology Co.; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Merck Serono Co. Ltd. K. Yoh: Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Lilly Japan; Honoraria (self): Novartis; Honoraria (self): Kirin; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): Taiho. H. Saka: Honoraria (self), Research grant/Funding (self): AstraZeneca. T. Kurata: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Eli lilly; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self): Ono; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai; Honoraria (self), Research grant/Funding (self): Bristol-Myers; Research grant/Funding (self): Takeda; Research grant/Funding (self): Novartis. Y. Ohe: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca, Chugai, ONO, Bristol-Myers Squibb; Research grant/Funding (self): Takeda; Advisory/Consultancy, Research grant/Funding (self): Kyorin; Advisory/Consultancy: Celltrion; Advisory/Consultancy: Amgen; Advisory/Consultancy: Nippon Kayaku; Honoraria (self): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self): Nippon Kayaku; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (self): Lilly; Research grant/Funding (self): Dainippon- Sumitomo; Research grant/Funding (self): Novartis; Research grant/Funding (self): Ignyta; Research grant/Funding (self): Kissei; Research grant/Funding (self): Daiichi-Sankyo, Janssen, Loxo. T. Hida: Honoraria (self): Ono Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Meyers Squibb; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Novartis. A. Mellemgaard: Full/Part-time employment: AstraZeneca. R.B. Verheijen: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca; Full/Part-time employment: Johnson&Johnson; Shareholder/Stockholder/Stock options: Aduro Biotech. X. Ou: Full/Part-time employment, Contracted with AstraZeneca through Phastar: AstraZeneca. M. Hayama, K. Sugibayashi: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. G. Oxnard: Honoraria (self): Foundation Medicine; Honoraria (self): Guardant Health; Honoraria (self): Sysmex; Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: DropWorks; Advisory/Consultancy: GRAIL; Advisory/Consultancy: Illumina; Advisory/Consultancy: Inviata; Advisory/Consultancy: Janssen; Advisory/Consultancy: Loxo; Advisory/Consultancy: Takeda; Licensing/Royalties, DCFI patent describing blood-based cancer monitoring: DFCI; Full/Part-time employment, Commencing June 15th: Foundation Medicine.

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e-Poster Display Session (ID 87) Poster Display

388P - Biosimilar TAB008 compared with bevacizumab in advanced non-squamous, non-small cell, EGFR wildtype lung cancer patients (ID 597)

Presentation Number
388P
Lecture Time
09:00 - 09:00
Speakers
  • Zhen Zhou (Shanghai, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, there is confirmed efficacy in many cancers.

Methods

In this randomized, double-blind, multicenter, phase III, treatment naive, locally advanced, metastatic, or recurrent EGFR wildtype non-squamous, non small cell lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received 4-6 (3 week)cycles of paclitaxel/carboplatin plus TAB008 or Avastin® at 15mg/kg intravenously, followed by 7.5mg/kg maintenance dose until disease progression, unacceptable toxicity, or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression free survival (PFS), 1 year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and pharmacological bio-equivalence of Cmin under steady state conditions.

Results

A total of 549 nsNSCLC patients were enrolled (277 in the TAB008 group, 272 in the Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008, and 55.720% for Avastin®, the 90% CI was 0.89-1.14, well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.7% vs 95.4%, p=0.8536), DoR (8.17 vs 7.3 months, p=0.3526), PFS (9.10 vs 7.97 months, p=0.9457), 1 year OSR (66.2 vs 68%, p=0.6793), or OS (20.4 vs 17.4 months, p=0.6594). Serious adverse events (AEs) occurred in 37.55% (104/277) and 34.32% (93/271) in the TAB008 and Avastin® groups. Anti-drug antibodies were reported in 3/277 (1.08%) and 5/271(1.85%) in the TAB008 and Avastin® groups. Steady-state trough concentrations (Cmin) were 106.13 and 96.03μg/mL in the TAB008 and Avastin® groups, with the treatment group ratio of LS geometric means is contained within the bioequivalence limits of 80.00–125.00% (90% CI: 101.74%-120.05%).

Conclusions

TAB008 is similar to bevacizumab(Avastin®) in terms of efficacy, safety, and pharmacokinetic parameters.

Legal entity responsible for the study

TOT BIOPHARM.

Funding

TOT BIOPHARM.

Disclosure

X. Li, L. Wang: Full/Part-time employment: TOT BIOPHARM. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

389P - Updated analysis from the KEYNOTE-042 China study: 1L pembrolizumab (pembro) vs chemotherapy (chemo) in Chinese patients (pts) with advanced NSCLC with PD-L1 TPS ≥1% (ID 642)

Presentation Number
389P
Lecture Time
09:00 - 09:00
Speakers
  • Yi-Long Wu (Guangzhou, Guangdong, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pembro monotherapy significantly improved OS vs chemo in PD-L1–positive (TPS ≥1%) locally advanced/metastatic NSCLC without targetable EGFR/ALK aberrations in the KEYNOTE-042 global study (NCT02220894) and in an analysis of Chinese pts from the KEYNOTE-042 global and China extension (NCT03850444) studies. Here we present an updated analysis of Chinese pts after ∼17 mo additional follow-up.

Methods

The global and extension studies were designed identically. Pts were randomized 1:1 (stratified by ECOG PS 0/1, squamous/nonsquamous histology, TPS ≥50%/1%‒49%) to up to 35 cycles of pembro 200 mg Q3W or up to 6 cycles of paclitaxel/pemetrexed + carboplatin with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in pts with PD-L1 TPS ≥50%, ≥20%, and ≥1%.

Results

262 Chinese pts with PD-L1–positive NSCLC were enrolled (global, n=92; China extension, n=170) and randomized to pembro (n=128) or chemo (n=134). As of Feb 21, 2020, median time from randomization to database cutoff was 33.0 (range, 25.6‒41.9) mo. Pembro improved OS vs chemo in all populations (Table); in pts with PD-L1 TPS ≥1%, the 24-mo rate for OS was 43.8% vs 28.2%, PFS was 15.6% vs 10.6%, and PFS2 was 26.4% vs 8.6%. Grade 3-5 drug-related AEs occurred in 19.5% of pembro-treated pts vs 68.8% of chemo-treated pts. In 22 pts who completed 35 cycles of pembro, ORR was 77.3% and median DOR was 27.6 mo. Additional efficacy and safety outcomes will be presented.

Conclusions

In this longer-term follow-up (∼3 y), 1L pembro monotherapy continued to improve OS with a manageable safety profile vs platinum-based chemo in Chinese pts with locally advanced/metastatic NSCLC without sensitizing EGFR/ALK aberrations and PD-L1 TPS ≥1%. Most pts who completed 2 y of pembro had durable responses. These findings support 1L use of pembro for PD-L1–positive advanced/metastatic NSCLC in China

n OS
Median (95% CI), mo HR (95% CI)
PD-L1 TPS ≥50% Pembro 72 24.5 (17.4–32.6) 0.63 (0.43–0.94)
Chemo 74 13.8 (10.1–18.3)
PD-L1 TPS ≥20% Pembro 101 21.9 (17.4–30.9) 0.66 (0.47–0.92)
Chemo 103 13.5 (10.1–17.9)
PD-L1 TPS ≥1% Pembro 128 20.2 (17.4–25.3) 0.67 (0.50-0.89)
Chemo 134 13.5 (10.1–17.9)

HR, hazard ratio.

.

Editorial acknowledgement

Writing support was provided by Michael S. McNamara, MS, ICON plc (North Wales, PA, USA) and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

Y-L. Wu: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim. L. Zhang: Research grant/Funding (self): Hengrui; Research grant/Funding (self): BMS; Research grant/Funding (self): Innovent Biologics. Q. Zhou: Honoraria (self): AstraZeneca; Honoraria (self): Roche. C. Zhou: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Eli Lilly; Honoraria (self): Hengrui, MSD; Honoraria (self): Sanofi; Honoraria (self): F. Hoffmann-La Roche Ltd.; Honoraria (self): Qilu. F. Souza: Full/Part-time employment: Merck & Co., Inc., Kenilworth, NJ, USA. J. Lin: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. J. Wang, B. Li: Full/Part-time employment: MSD China. T. Mok: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Clovis Oncology; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche/Genentech; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): SFJ Pharmaceuticals; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Taiho; Research grant/Funding (self): XCovery; Honoraria (self), Speaker Bureau/Expert testimony: Amoy Diagnostics Co. Ltd.; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Speaker Bureau/Expert testimony: InMed Medical Communication; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Honoraria (self), Speaker Bureau/Expert testimony: PRIME Oncology; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Virtus Medical Group; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda Oncology; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Biolidics Ltd.; Shareholder/Stockholder/Stock options: Hutchison ChiMed, Loxo-Oncology; Advisory/Consultancy, Shareholder/Stockholder/Stock options: OrigiMed; Shareholder/Stockholder/Stock options: Sanomics Ltd.; Advisory/Consultancy: ACEA Biosciences Inc; Advisory/Consultancy: Alpha Biopharma Co., Ltd.; Advisory/Consultancy: Bayer; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Incyte Corporation; Advisory/Consultancy: Celgene; Advisory/Consultancy: Cirina; Advisory/Consultancy: CStone Pharmaceuticals; Advisory/Consultancy: Fishawack Facilitate Ltd.; Advisory/Consultancy: geneDecode Co. Ltd.; Advisory/Consultancy: Hengrui Therapeutics; Advisory/Consultancy: Ignyta Inc.; Advisory/Consultancy: IQVIA; Advisory/Consultancy: Janssen; Advisory/Consultancy: Loxo-Oncology; Advisory/Consultancy: MoreHealth; Advisory/Consultancy: OncoGenex Technologies Inc.; Advisory/Consultancy: Sanofi-Aventis; Advisory/Consultancy: Vertex Pharmaceuticals; Advisory/Consultancy: Yuhan Corp; Leadership role: ASCO; Leadership role: CSCO; Leadership role: IASLC. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

391P - Economic impact of next-generation sequencing (NGS) versus single-gene testing modalities to detect genomic alterations (GAs) in metastatic non-small cell lung cancer (mNSCLC) in Asia (ID 348)

Presentation Number
391P
Lecture Time
09:00 - 09:00
Speakers
  • Herbert Ho Fung Loong (Sha Tin, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The economic impact of using NGS vs. single-gene testing strategies in patients (pts) with mNSCLC have substantial implications on healthcare resource allocation. Pennell et al. (JCO PO 2019) have shown the use of upfront NGS testing in pts with mNSCLC was associated with substantial cost savings and shorter time-to-test results in the United States. Such conclusions may not necessarily apply in other jurisdictions where the prevalence of pts with actionable mutations, cost of healthcare and reimbursement models differ. Taking Hong Kong (HK) as an example, we assess the economic impact of NGS vs. single-gene testing in Asia.

Methods

A decision analytical model was built to compare sequential (SE), panel (PA), exclusionary (EX), and upfront NGS testing in pts with newly diagnosed mNSCLC. In SE and PA, pts were tested for GAs with approved treatment (EGFR, ALK, ROS1, BRAF) followed by SE or NGS for other GAs. In EX, EGFR and ALK were tested first, followed by NGS. 2.4 % of pts were assumed to receive re-biopsy and 25% to continue testing for non-actionable GAs. For each modality, mutation identified, time to receive testing results, and costs (2019 USD) were estimated. Sensitivity analyses (SAs) was used to test model robustness.

Results

For Hong Kong (∼7.3M population), EX required the shortest time to receive results (1.5 weeks) and was most cost-saving compared to other modalities. If all pts use EX, $3.0M cost saving will be achieved compared with current practice, with 96.1% of actionable and 46.5% of non-actionable GA being detected. If all pts use NGS, it will cost an additional $4.5M to payer with a 100% GA detection rate. The results were sensitive to NGS price and the % of pts continued testing for non-actionable GAs.

Conclusions

As opposed to findings by Pennell et al., EX rather than upfront NGS is the best option in terms of cost and time to results in HK. This is also applicable for other Asia countries as this is driven by higher prevalence of mNSCLC pts with EGFR mutations in the Asian population. EX, however, does not capture all possible GAs. As more GA become actionable and NGS testing costs reduce, NGS may potentially be a cost saving option.

Legal entity responsible for the study

Novartis Corporation.

Funding

Has not received any funding.

Disclosure

H. Loong: Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer-Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eli-Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ignyta; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy, No honorarium or specific COI to this specific study: Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/Funding (institution): MSD; Research grant/Funding (institution): Mundipharma; Speaker Bureau/Expert testimony: Abbvie; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Guardant Health. C.P.K. Chan, A. Chang, M. Gibbs: Full/Part-time employment: Novartis. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

392P - Clinical data from the real world: Efficacy analysis of ceritinib (450mg) in ALK-positive non-small cell lung cancer patients with brain metastases in China (ID 360)

Presentation Number
392P
Lecture Time
09:00 - 09:00
Speakers
  • Zhixin Qiu (Chengdu, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The real-world intracranial efficacy data of ceritinib at a dose of 450mg QD are still unavailable, thus this study aims to analyze the intracranial efficacy of ceritinib (450mg QD) in ALK-rearrangement NSCLC patients in China.

Methods

The intracranial and whole body efficacies [objective response rate (ORR) and disease control rate (DCR)] were respectively evaluated according to the Response Assessment in Neuro-Oncology (RANO) and Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) standards, along with progression-free survival (PFS)/survival time and adverse events (AEs) obtained through follow-ups.

Results

A total of 57 ALK-rearrangement NSCLC patients with brain metastases (BM) were enrolled in this study. Among them, 53 patients experienced progression at baseline during or after prior crizotinib, and 24 patients received prior brain radiotherapy. The intracranial ORR and DCR were 73.7% and 93.0%, respectively. The whole body ORR and DCR were 87.7% and 98.2%, respectively. The median intracranial PFS and median whole body PFS in patients reached the endpoint were 8.75 months and 7.6 months, respectively; while those in all patients were not reached and predicted to be not evaluable (NE) (intracranial: 95% CI: 12.9-NE and whole body: 95% CI: 15.2-NE). The estimated 12-month event-free probabilities (EFP) of intracranial lesions was 68.1% ; and these of whole body lesions was 74.7%. Subgroup analysis showed the estimated 12-month EFP of intracranial lesions was relatively higher in patients with prior brain radiotherapy (93.8% vs 47.1%, P=0.0006). Additionally, we reported a 74-year-old female ALK-rearrangement NSCLC patient with BM achieved continuous response (intracranial PFS: 12.9 months) to ceritinib reduced to 150mg QD due to intolerable AE and administered for 7.5 months.

Conclusions

Ceritinib administered at a dose of 450mg QD to ALK-rearrangement NSCLC patients with BM in China demonstrates superior ORR and DCR, as well as PFS and EFP that are expected to be improved. Especially the estimated 12-month EFP of intracranial lesions was improved in patients with prior brain radiotherapy.

Legal entity responsible for the study

West China Hospital, SIchuan Universtiy.

Funding

National Science Foundation of China (81700095, 81870034).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

393P - Clinical characteristics and prognosis of patients with pulmonary mucoepidermoid carcinoma: A SEER-based analysis (ID 364)

Presentation Number
393P
Lecture Time
09:00 - 09:00
Speakers
  • Lingxiao Qiu (Zhengzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pulmonary mucinous epidermoid carcinoma (PMEC) is malignant and extremely rare. With only few case reports or small case series are reported, the prognosis of PMEC is not fully understood. In this study, we aimed to evaluate the prognostic factors of PMEC and to establish a prognostic nomogram model to predict its cancer-specific survival (CSS).

Methods

Within the Surveillance, Epidemiology, and End Results (SEER) Database from its inception to December 31, 2016, patients diagnosed with PMEC were retrospectively identified. Kaplan–Meier analysis and Cox regression were performed to evaluate the CSS stratified by different covariates. A predictive model of nomograms was conducted and the Concordance index (C-index) and calibration curves were used to validate the model.

Results

A total of 585 PMEC patients are identified. The 5-, 10-, and 20-year CSS of stage I-II PMEC were 96.0%, 91.4%, and 88.9%, respectively. The 1-, 3-, 5-, and 10-year CSS of stage III-IV PMEC were 56.5%, 39.45%, 32.1%, 29.4%, respectively. The results of survival curves showed that patients with older ages, larger tumor sizes, bilateral tumors, poorer differentiation and higher stage of T, N and M aligned with poorer prognosis. Surgical treatment significantly improved the patients’ CSS (P < 0.001). But combined therapy didn't present better CSS results than surgery alone did. The multivariate COX results revealed that the covariates of age, bilateral tumor, tumor sizes, pathological differentiation grade, T stage, N stage, M stage and therapy were independent prognosis factors for PMEC. These factors were used to construct a nomogram. The C-index of the nomogram was 0.921. The calibration curve showed that favorable consistency between the predicted PMEC CSS and the actual observation. Validation of the nomogram was conducted with the validation cohort. The C-index of validation was 0.968, and the calibration curve showed favorable consistency.

Conclusions

Age, bilateral tumor, tumor sizes, pathological differentiation grade, T stage, N stage, M stage, and therapy were independent prognosis factors of PMEC patients. A nomogram on predicting the CSS of PMEC was first built and validated, showing its potential value in practice.

Legal entity responsible for the study

Lingxiao Qiu.

Funding

The National Natural Science Foundation of China (No.81874042).

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

394P - Apatinib plus etoposide capsules as third-line or further-line treatment for extensive stage small cell lung cancer patients: A multicenter, single arm, phase II clinical trial (ID 380)

Presentation Number
394P
Lecture Time
09:00 - 09:00
Speakers
  • Zhen He (Zhengzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Advanced small cell lung cancer patients have very poor outcome, with a median overall survival (OS) of less than 1 year. We conducted this phase II clinical trial to evaluate the efficacy and safety of apatinib plus etoposide capsules in the third-line or further-line treatment of patients with extensive stage small cell lung cancer.

Methods

Patients with extensive stage small cell lung cancer who failed ≥ 2 lines of therapy were recruited from 11 hospital across China. All participants should have an Eastern Cooperative Oncology Group performance status of 0 to 2, at least one evaluable lesion according to response evaluation criteria in solid tumor (RESCIST 1.1). Participants received apatinib (250mg orally every day) and etoposide capsules (50mg orally from day 1 to 21, every 4 weeks) until disease progression, death or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS) and safety.

Results

Totally 52 patients with a median age of 60.5 (range, 30-77) years, including 40 men (77.0%) were enrolled in our study from December 2017 to August 2019. By the end of December 2019, 45 patients progressed and 36 died. Among 52 evaluable patients, 34 patients showed a stable disease, 11 patients achieved a partial response, showing an objective response rate (ORR) of 21.2% and disease control rate (DCR) of 86.5%. The median follow-up duration was 6.6 months. The median PFS was 3.3 months (95% CI, 2.56-4.05), and median OS was 4.5 months (95% CI, 3.50-4.90). 1-year survival rate was 11.54%. Major adverse events (AEs) included leukopenia (30.77%), anemia (25%), and fatigue (19.23%). No grade 3 or more AEs were reported.

Conclusions

Apatinib plus etoposide capsules showed reasonable efficacy and toxicity among extensive stage small cell lung cancer patients in third-line or above setting. Further exploration of apatinib in phase Ⅲ trials is warranted.

Clinical trial identification

NCT03389087.

Legal entity responsible for the study

The authors.

Funding

Jiangsu Hengrui Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

395P - Afatinib in Asian and non-Asian patients (pts) with EGFR mutation positive (EGFRm+) NSCLC harboring major uncommon mutations (ID 392)

Presentation Number
395P
Lecture Time
09:00 - 09:00
Speakers
  • James Chih-Hsin Yang (Taipei City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Uncommon EGFR mutations show heterogeneity in their EGFR TKI sensitivities.1 Afatinib has shown broad inhibitory activity against uncommon mutations in vitro,1 and clinical activity against major uncommon mutations (G719X/L861Q/S768I).2 However, clinical data regarding the efficacy of afatinib against other uncommon EGFR mutations are lacking, particularly between ethnicities.

Methods

This pooled analysis assessed afatinib activity in Asian/non-Asian, EGFR TKI-naïve pts with NSCLC and uncommon EGFR mutations, treated in RCTs and real-world studies. Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I); compound mutations (≥2 uncommon mutations); and other uncommon mutations. Key endpoints were overall response rate (ORR), duration of response (DoR), and time to treatment failure (TTF).

Results

Of the 178/120 Asian/non-Asian pts with uncommon EGFR mutations, 62/35% had a major uncommon mutation (G719X only: 20/20%; L861Q only: 26/8%; S768I only: 3/4%), 16/39% had an Ins20 mutation. Clinical activity (Asian/non-Asian) was observed against major uncommon mutations (ORR: 66/59%; median DoR: 14.7/15.9 mos; G719X: 62/65%; L861Q: 60/50%; S768I: 80/25%), compound mutations (ORR: 81/100%; median DoR: 11.5/18.6 mos) and other uncommon mutations (ORR: 79/60%; median DoR: 9.0/10.7 mos). Some pts with Ins20 responded (21/23%). TTF was longest in pts with compound mutations, particularly non-Asian pts (median 18.5 mos).

Conclusions

Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity. Asian pts appeared to have a high proportion of major uncommon mutations, known to be highly sensitive to afatinib.2 1. Kohsaka S, et al. Sci Transl Med 2017;9:eaan6566 2. Yang JC, et al. Lancet Oncol 2015;16:830‒8

Patients*, n (%) ORR, % TTF, mos (95% CI)
Asian (N=178) Non-Asian (N=120) Asian Non-Asian Asian Non-Asian
Major uncommon (MU) 110 (61.8) 42 (35.0) 66 59 11.5 (11.5, 13.8) 9.0 (4.6, 15.4)
G719X 36 (20.2) 24 (20.0) 62 65 11.5 (9.6, 17.1) 9.0 (3.2, 18.7)
L861Q 46 (25.8) 9 (7.5) 60 50 11.5 (11.1, 11.5) 5.7 (1.4, 10.7)
S768I 5 (2.8) 5 (4.2) 80 25 NR (2.6, NR) 15.6 (3.0, 20.7)
Compound 26 (14.6) 8 (6.7) 81 100 11.5 (8.2, 16.6) 18.5 (1.6, NR)
Ins20 29 (16.3) 47 (39.2) 21 23 4.5 (2.6, 5.4) 3.9 (2.8, 5.4)
Any de novo T790M 19 (10.7) 14 (11.7) 38 17 4.7 (1.2, 5.5) 2.9 (0.9, 6.7)
Other 17 (9.6) 13 (10.8) 79 60 7.2 (1.8, 11.9) 10.7 (2.0, 24.0)

*Patients may be included in >1 group; Includes patients with MU + Del19/L858R compound mutations.

.

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Nadia Fowler, of GeoMed, an Ashfield company, part of UDG Healthcare plc.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: MSD Oncology; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Brueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Snakyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda Oncology; Honoraria (institution), Advisory/Consultancy: Incyte; Honoraria (institution), Advisory/Consultancy: H: Boehringer Ingelheim; Roche; MSD; AstraZeneca; Novartis; Bristol-Myers Squibb; Ono Pharmaceutical; Takeda Oncology; Eli Lilly; Pfizer. M. Schuler: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Honoraria (self): Amgen; Honoraria (self): MSD; Honoraria (self): Pierre Fabre. S. Popat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AZ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Paradox; Research grant/Funding (institution): Ariad. S. Miura: Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Taiho Pharma; Speaker Bureau/Expert testimony: Ono Pharma; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin. S. Heeke: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Qiagen; Travel/Accommodation/Expenses: Roche. A. Passaro: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Dako. K. Park: Advisory/Consultancy: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AZ; Advisory/Consultancy, Speaker Bureau/Expert testimony: BI; Advisory/Consultancy: BMS; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: JNJ; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Research grant/Funding (self): MSD Research. E.S. Kim: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Takeda; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

396P - Efficacy and safety of S-1 in elderly patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy: A subgroup analysis of the EAST-LC (ID 584)

Presentation Number
396P
Lecture Time
09:00 - 09:00
Speakers
  • James Chih-Hsin Yang (Taipei City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

EAST-LC (JapicCTI-101155) was a randomized phase III trial conducted in East Asia that demonstrated the non-inferiority of oral S-1 to docetaxel (DTX) in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC) [H. Nokihara and S. Lu, Annals of Oncology (2017)]. Here, we report the results of elderly pts (EP) subgroup.

Methods

The key inclusion criteria were as follows: age ≥18 years; an ECOG performance status (PS) of 0 to 2; and ≤ 2 previous chemotherapy regimens, including a platinum-based one [if pts had received gefitinib or erlotinib, then three regimens were allowed]. Eligible pts were randomized 1:1 to receive S-1 (80-120 mg/day; days 1-28 in a 6-week cycle) or DTX (60 mg/m2 in Japan, 75 mg/m2 at the other sites; day 1 in a 3-week cycle). EP were defined as aged ≥ 70 years and evaluated the efficacy, safety and quality of life (QOL), using the EORTC QLQ-C30. The primary endpoint of the trial was overall survival (OS).

Results

A total of 190 EP were subjects to this analysis (90 in the S-1 arm and 100 in the DTX arm). There were no significant differences between both arms in terms of baseline characteristics, except for ECOG PS (P = 0.0132). Disease progression was the most common reason for treatment discontinuation in both arms (63.6% and 51.5% in S-1 and DTX arms, respectively), followed by adverse events (AEs) (13.6% and 24.2%). The median OS were 14.7 months versus 12.1 months; HR 0.76 (95% CI: 0.54–1.07) for S-1 versus DTX, respectively. The most common treatment-related AEs were decreased appetite (61.4%), diarrhea (47.7%) and pigmentation (39.8%) in the S-1 arm, and neutropenia (66.7%), alopecia (49.5%) and leukocytopenia (47.5%) in the DTX arm, respectively. The adjusted mean score difference (S-1 – DTX) of EORTC QLQ-C30 global health status until 48 weeks was 7.41 (95% CI: 0.37–14.46).

Conclusions

S-1 was showed the comparable efficacy, safety and QOL to DTX in previously treated EP with advanced NSCLC, and the results were consistent to those of the overall EAST-LC population. These results could support the usage of S-1 as a viable treatment option for EP.

Clinical trial identification

JapicCTI-101155.

Legal entity responsible for the study

Taiho Pharmaceutical.

Funding

Taiho Pharmaceutical.

Disclosure

J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: MSD Oncology; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda Oncology; Honoraria (institution), Advisory/Consultancy: Incyte. T.S.K. Mok: Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Officer/Board of Directors: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): SFJ Pharmaceuticals; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Sanomics; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Takeda; Advisory/Consultancy, Officer/Board of Directors: Chi-Med; Honoraria (self), Advisory/Consultancy: ACEA Biosciences; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Merck Serono; Research grant/Funding (institution): XCovery; Honoraria (self), Advisory/Consultancy: Ignyta; Honoraria (self), Advisory/Consultancy: ertex Pharmaceuticals. S. Lu: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Hutchison; Research grant/Funding (self): BMS; Research grant/Funding (self): Heng Rui ; Research grant/Funding (self): Beigene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self): Hansoh; Honoraria (self): Hengrui Therapeutics; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: MediPharma; Advisory/Consultancy: Simcere; Advisory/Consultancy: ZaiLab; Advisory/Consultancy: GenomiCare; Advisory/Consultancy: Yuhan Corporation; Advisory/Consultancy: PrIME Oncology. K. Nakagawa: Honoraria (self), Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (institution): Astellas Pharma Inc.; Honoraria (self), Research grant/Funding (institution): MSD K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer Japan Inc.; Honoraria (self), Advisory/Consultancy: Kyorin Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd.; Honoraria (self): Nichi-Iko Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb Company; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan K.K.; Research grant/Funding (institution): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Daiichi Sankyo Co., Ltd.; Honoraria (self): Nippon Kayaku Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Merck Serono Co., Ltd./ Merck Biopharma Co., Ltd.; Honoraria (self), Research grant/Funding (institution): AbbVie Inc. N. Yamamoto: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Daiichi Sankyo Company; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda Pharmaceutical Co. Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self), Research grant/Funding (institution): Eli Lilly Japan K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Boehringer-Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Pfizer Inc.; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Nippon Kayaku; Honoraria (self), Advisory/Consultancy: Merck Biopharma Co., Ltd; Research grant/Funding (self), Research grant/Funding (institution): Astellas Pharma Inc; Research grant/Funding (self), Research grant/Funding (institution): Tsumura & Co.; Research grant/Funding (self), Research grant/Funding (institution): AbbVie GK.; Research grant/Funding (institution): Amgen Inc; Research grant/Funding (institution): Kyorin Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Eisai Co., Ltd. L. Zhang: Research grant/Funding (institution): Roche; Research grant/Funding (institution): BMS; Honoraria (self): MSD; Research grant/Funding (institution): Henrui Pharm. R.A. Soo: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self): Amgen; Honoraria (self): Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Taiho; Honoraria (self): Takeda; Honoraria (self): Yuhan. S. Morita: Honoraria (self): AstraZeneca K.K.; Honoraria (self): Bristol-Myers Squibb Company; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K; Honoraria (self): MSD K.K.; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim Co. Ltd.; Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Taiho Pharmaceutical Co. Ltd. T. Tamura: Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self): Chugai; Honoraria (self): Eli Lilly; Honoraria (self): Nippon Kayaku; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Ono; Honoraria (self): MSD; Honoraria (self): Cmic Shift-Zero. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

397P - A phase I cohort expansion trial of OBI-833 in non-small cell lung cancer patients (ID 680)

Presentation Number
397P
Lecture Time
09:00 - 09:00
Speakers
  • Ching-Liang Ho (Taipei city, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

OBI-833 is a novel cancer vaccine targeting a tumor-associated carbohydrate antigen, Globo H. Results of the dose-escalation trial, which showed a favorable safety profile, supported the following cohort expansion trial in non-small cell lung cancer (NSCLC) patients at a dose of 30 μg.

Methods

Patients with Globo H-positive metastatic NSCLC who have achieved stable disease (SD), or partial response (PR) after at least one regimen of anticancer therapy were enrolled. For patients who were on the targeted therapy, OBI-833 was added to their ongoing therapies. Humoral immune responses and relevant tumor biomarkers were monitored.

Results

A total of 14 patients were successfully enrolled. Treatment is ongoing for five patients. Nine patients have been discontinued. Eleven patients were treated with a 1st or 2nd-generation EGFR TKI and OBI-833, one patient with ceritinib plus OBI-833, and two patients with OBI-833 monotherapy. As of June 2020, a total of 79 treatment-related AEs were reported. Most were injection site reactions. Among the 6 reported SAEs, one was treatment-related, which was Grade 4 acute pancreatitis, and five were non-treatment related. The Globo H expression of the tumor specimens was evaluated by IHC and reported as H score. At the H score cutoffs of 0 and 100, 71% (17/24) and 50% (12/24) of the screened patients were Globo H positive, respectively. Thirteen (93%) and nine (64%) patients showed blood levels of anti-Globo H IgM and IgG. The positivity was defined as the anti-Globo H IgM or IgG concentration ≥ 3 μg/mL at least once during the study period. Median PFS was 31 weeks (range, 3–108). Six of the 11 EGFR TKI-treated patients had SD for over six months. One patient has been treated for more than two years and his treatment is still ongoing. Of note, one patient’s tumor size had reduced by 27% after 16 months of OBI-833 treatment. Plasma EGFR mutation load was significantly reduced from 8.57 to 0 in another patient.

Conclusions

OBI-833 can elicit a beneficial immune response in NSCLC patients and had rendered some TKI-treated patients durable stable disease status. Further development of OBI-833 in EGFR-mutated NSCLC patients to assess the potential benefits of combination therapy of OBI-833 with TKIs is ongoing.

Clinical trial identification

NCT02310464.

Legal entity responsible for the study

The authors.

Funding

OBI Pharma.

Disclosure

C-C. Ou, C-E. Tsai: Full/Part-time employment: OBI Pharma. P-C. Yang: Advisory/Consultancy: OBI Pharma. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

398P - Real-world mechanism of crizotinib-resistance in MET exon 14 skipping mutations non-small-cell lung cancer using next generation sequencing: A multicenter study (ID 883)

Presentation Number
398P
Lecture Time
09:00 - 09:00
Speakers
  • Dong Wang (Nanjing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

MET exon 14 skipping is a potential driver alteration in lung cancer targetable. Treatment with crizotinib can cause dramatic responses in patients whose cancers have MET exon 14 skipping. The mechanism of acquired resistance to crizotinib for the patients with MET exon 14 skipping NSCLC is not yet fully identified. In this study, we performed mutational profiling in a cohort of MET exon 14 skipping NSCLC patients at diagnosis and following acquired resistance to crizotinib using targeted NGS.

Methods

We screened 2926 patients with NSCLC for MET exon 14 skipping mutation. Among them, 14 patients received crizotinib treatment, and a total of 9 patients with stage IIIb-IV MET exon 14 skipping mutation NSCLC underwent tumor biopsies or blood withdrawal by the time of acquiring resistance to crizotinib, including 3 formalin-fixed paraffin-embedded (FFPE) samples, 4 serum samples and 2 serous effusions. We used targeted NGS to detect the gene status of patients.

Results

In total, we identified 41 genetic alterations with a median of 4.6 mutations per patient. 88.9% of patients still exhibit MET exon 14 skipping mutation, and 22.2% of patients acquired MET point mutations. Besides other known resistance mechanisms, we identified HRAS mutation in 11.1% of patients, and EGFR mutation in 11.1%. Interestingly, we also observed NUP93, MS4A1 and ELAC2 mutations in MET acquired point mutation-negative patients, which were restricted to crizotinib resistance.

Conclusions

MET exon 14 skipping patients acquired resistance mutational profiles were uncovered, and this study also comprehensively depicted the genetic landscape in a Chinese MET exon 14 skipping NSCLC population resistant to crizotinib. Precision methods, such as NGS for oncogenic alteration detection for further study of resistance and suggests corresponding relevant tactics against the challenge of disease progression.

Legal entity responsible for the study

Chun-wei Xu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

399P - Real-world insights into patients (pts) with advanced NSCLC and MET alterations (ID 330)

Presentation Number
399P
Lecture Time
09:00 - 09:00
Speakers
  • Marisa Bittoni (Columbus, AL, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pts with NSCLC and MET exon 14 skipping (METex14; 3–4%) or MET amplification (METamp; 1–2%) have not been well characterized; this study aimed to address this gap.

Methods

This non-interventional descriptive cohort study used real-world data extracted from electronic medical records from academic oncology centers in Israel, The Netherlands, Taiwan, and the USA. Pts had confirmed diagnosis of advanced (stage IIIB–IV) NSCLC (date of diagnosis=index date) between 1 Jan 2010 and 30 Sept 2018 and MET alterations. Medical history was assessed prior to and at the index date (baseline period) and outcomes from first date of treatment to death, loss to follow-up, or end of the study period.

Results

70 pts had METex14 tumors and 47 pts had METamp tumors; testing methods were heterogenous. Concomitant oncogenic mutations were more common in METamp than METex14 pts; 9% of METex14 pts had concomitant METamp. Records of systemic therapy for advanced disease were available for 58 (83%) pts in the METex14 cohort and 36 (77%) pts in the METamp cohort. Common treatments (METex14 vs METamp) were platinum-based therapy (1st line [1L], 44 vs 41%; 2nd line [2L], 35 vs 30%) and MET inhibitor monotherapy (1L, 33 vs 29%; 2L, 30 vs 39%). Immune checkpoint inhibitors (±chemotherapy) were used across 1L (13 vs 16%) and 2L (35 vs 13%). Median (95% CI) time to next treatment or death was 6.3 months (4.8, 10.9) for 1L (n=52) and 7.8 months (3.9, 11.3) for 2L (n=23) in the METex14 cohort and 9.0 months (6.1, 11.7) for 1L (n=34) and 5.1 months (3.3, 12.8) for 2L (n=23) in the METamp cohort. Median (95% CI) overall survival from start of 1L therapy (any) was 12.0 months (6.8, 19.2) in METex14 and 22.0 months (9.8, 31.2) in the METamp cohort

METex14 (n=70) METamp (n=47)
Biopsy method; liquid/tissue 81%/20% 77%/26%
Age, median (range); years 74 (37, 92) 63 (37, 87)
Gender, male 51% 68%
Race: White Asian Other 59% 34% 7% 85% 4% 11%
Smoking history (ever smokers) 49% 79%
Advanced disease at diagnosis 83% 65%
Histology: Adenocarcinoma squamous cell carcinoma sarcomatoid 84% 1% 6% 82% 4% 2%
Brain metastases* 19% 25%
Comorbidity: Uncomplicated diabetes peripheral vascular disease chronic obstructive pulmonary disease 10% 9% 9% 6% 2% 13%

Patient records were from Israel (n=18), The Netherlands (n=13), Taiwan (n=23), and the USA (n=63). *Data on brain metastases were available for 52 pts in the METex14 cohort and 28 pts in the METamp cohort.

.

Conclusions

Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in pts with METex14 who were older and had more advanced disease at diagnosis. Screening for these alterations in pts with advanced NSCLC is warranted.

Editorial acknowledgement

Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany.

Disclosure

J.C-H. Yang: Advisory/Consultancy, personal fees: Boehringer Ingelheim; Advisory/Consultancy, personal fees: Eli Lilly; Advisory/Consultancy, personal fees: Bayer; Advisory/Consultancy, personal fees: Roche/Genentech; Advisory/Consultancy, personal fees: Chugai Pharmaceutical; Advisory/Consultancy, personal fees: MSD; Advisory/Consultancy, personal fees: Pfizer; Advisory/Consultancy, personal fees: Novartis; Advisory/Consultancy, personal fees: BMS; Advisory/Consultancy, personal fees: Ono Pharmaceuticals; Advisory/Consultancy, personal fees: AstraZeneca; Advisory/Consultancy, personal fees: ACT Genomics; Advisory/Consultancy, personal fees: Merck Serono; Advisory/Consultancy, personal fees: Celgene; Advisory/Consultancy, personal fees: Yuhan Pharmaceuticals; Advisory/Consultancy, personal fees: Daiichi Sankyo; Advisory/Consultancy, personal fees: Hansoh Pharmaceuticals; Advisory/Consultancy, personal fees: Takeda Pharmaceuticals; Advisory/Consultancy, personal fees: Blueprint Medicines; Advisory/Consultancy, personal fees: Amgen. J-Y. Shih: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Chugai Takeda; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Gaurdant360; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): NovellusDx; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Takeda. E. Smit: Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Takeda; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics. R. Camidge: Advisory/Consultancy: Anchiarno; Advisory/Consultancy: Amgen; Advisory/Consultancy, Leadership role, Research grant/Funding (self), Principle investigator for company sponsored trials (institution): Takeda; Advisory/Consultancy: Roche; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Pfizer; Advisory/Consultancy: CBT Pharmaceuticals; Advisory/Consultancy, Interstitial Lung Disease adjudication committee: Daiichi-Sankyo; Advisory/Consultancy, data safety monitoring board: G1 Therapeutics; Advisory/Consultancy, data safety monitoring board: Bio-Thera; Advisory/Consultancy: Blueprint; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Abbvie; Advisory/Consultancy: Achilles; Advisory/Consultancy: BeyondSpring; Advisory/Consultancy, standing Scientific Review Committee: Apollomics; Advisory/Consultancy, standing Scientific Review Committee: 14ner/Elevation; Advisory/Consultancy: Archer; Advisory/Consultancy: Helssin; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Bristol-Myers Squibb; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Medtronic; Advisory/Consultancy: Ribon; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): AstraZeneca; Advisory/Consultancy: Arrys/Kyn; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Hengrui; Advisory/Consultancy, Scientific Review Committee and Principle investigator for company sponsored trials (institution): Hansoh; Advisory/Consultancy, Leadership role, Principle investigator for company sponsored trials (institution): Roche/Genentech; Advisory/Consultancy: Inivata; Leadership role, Principle investigator for company sponsored trials (institution): GlaxoSmithKline; Leadership role, Principle investigator for company sponsored trials (institution): Inhibrx; Leadership role, Principle investigator for company sponsored trials (institution): Lycera; Leadership role, Principle investigator for company sponsored trials (institution): MedImmune; Leadership role, Principle investigator for company sponsored trials (institution): Merck; Leadership role, Principle investigator for company sponsored trials (institution): Pfizer; Leadership role, Principle investigator for company sponsored trials (institution): Phosplatin; Leadership role, Principle investigator for company sponsored trials (institution): Psioxus; Leadership role, Principle investigator for company sponsored trials (institution): Rain; Leadership role, Principle investigator for company sponsored trials (institution): Seattle Genetics; Leadership role, Principle investigator for company sponsored trials (institution): Symphogen; Leadership role, Principle investigator for company sponsored trials (institution): Tolero. D. Carbone: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Nexus Oncology; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bayer; Advisory/Consultancy: Biothera; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Helsinn Therapeutics; Advisory/Consultancy: Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Peregrine Pharmaceuticals; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Synta. D. Oksen, E. Boutmy, A. Johne: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. P. Paik: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Calithera; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: Takeda; Research grant/Funding (self), Research grant/Funding (institution): EMD Serono. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

400P - Sequential afatinib and osimertinib in real-world EGFR mutation positive (EGFRm+) NSCLC: Final analysis of Asian patients in the GioTag study (ID 452)

Presentation Number
400P
Lecture Time
09:00 - 09:00
Speakers
  • Maximilian J. Hochmair (Vienna, Austria)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Second- (afatinib and dacomitinib) and third-generation (osimertinib) EGFR tyrosine kinase inhibitors (TKIs) have demonstrated superior efficacy versus the first-generation EGFR TKIs (erlotinib and gefitinib) for EGFRm+ NSCLC. However, TKI resistance is inevitable and up to 75% of afatinib-treated patients develop the T790M mutation. Hence, questions remain about the optimal sequence of EGFR TKIs. The observational GioTag study investigated outcomes in patients with EGFRm+ NSCLC treated with sequential afatinib and osimertinib in a ‘real-world’ setting. Time to treatment failure (TTF) and overall survival (OS) were encouraging (Hochmair et al Future Oncol 2019). Here, we report final TTF and OS data for Asian patients.

Methods

Data were retrospectively collected for patients with EGFRm+ (Del19, L858R) NSCLC who had T790M+ disease after first-line afatinib and then received osimertinib. TTF was the primary outcome; OS analysis was exploratory.

Results

203 patients were included in the global GioTag study; of these, 50 were Asian. After a median follow-up of 33.9 months, median TTF was 37.1 months (90% CI: 28.1–40.3) and median OS was 44.8 months (90% CI: 37.0–57.8) in Asian patients (overall global study population: median TTF 27.7 months [90% CI: 26.7–29.9], median OS 37.6 months [90% CI: 35.5–41.3]). Clinical benefit was particularly encouraging in Asian patients with Del19-positive disease (n=31): median TTF 40.0 months (90% CI: 36.4–45.0), median OS 45.7 months (90% CI: 38.2–57.8). Median TTF and OS were 38.2 months (90%: 28.9–40.3) and 44.8 months (90% CI: 38.2–57.8), respectively, in Asian patients who received a starting dose of afatinib 40 mg (n=46), and 36.4 months (90% CI: 28.1–41.7) and 41.3 months (90% CI: 36.9–57.8), respectively, in Asian patients with ECOG performance status 0/1 (n=45).

Conclusions

In a real-world clinical practice setting, sequential afatinib and osimertinib is effective, particularly in Asian patients with EGFRm+ NSCLC who develop T790M. Median OS was nearly 4 years in those with Del19+ disease, suggesting sequential TKI use could potentially allow these patients to receive long-term chemotherapy-free treatment.

Clinical trial identification

NCT03370770.

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Jane Saunders, of GeoMed, an Ashfield company, part of UDG Healthcare plc.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

M.J. Hochmair: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. A. Morabito: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Takeda; Honoraria (self): BMS; Honoraria (self): MSD. D. Hao: Advisory/Consultancy: Roche; Honoraria (self), Research grant/Funding (self): AstraZeneca; Research grant/Funding (self), Travel/Accommodation/Expenses: Boehringer Ingelheim. C-T. Yang: Advisory/Consultancy: BI; Advisory/Consultancy: MSD; Advisory/Consultancy: Ono; Advisory/Consultancy: Chugai; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. R.A. Soo: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Eli Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Taiho; Honoraria (self): Takeda; Honoraria (self): Yuhan; Honoraria (self): Amgen. J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: MSD Oncology; Honoraria (institution), Advisory/Consultancy: Merck Sernono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Brueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Snakyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda Oncology; Honoraria (institution), Advisory/Consultancy: Incyte; Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Roche; MSD; AstraZeneca; Novartis; Bristol-Myers Squibb; Ono Pharmaceutical; Takeda Oncology; Eli Lilly; Pfizer. B. Halmos: Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Astra-Zeneca; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy: Spectrum; Advisory/Consultancy, Research grant/Funding (self): Takeda; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Amgen; Advisory/Consultancy, Research grant/Funding (self): Guardant Health; Advisory/Consultancy: Foundation One; Advisory/Consultancy: TPT; Research grant/Funding (self): Eli-Lilly; Research grant/Funding (self): GSK; Research grant/Funding (self): Mirati; Research grant/Funding (self): AbbVie. A. Märten: Full/Part-time employment: Boehringer Ingelheim. T. Cufer: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

401P - A prospective, phase II trial of low-dose afatinib monotherapy for patients with EGFR, mutation-positive, non-small cell lung cancer (TORG1632) (ID 526)

Presentation Number
401P
Lecture Time
09:00 - 09:00
Speakers
  • Satoshi Igawa (Kanagawa, Minami-li, Sagamihara, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Afatinib is an efiective treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), however, its toxicities often require dose modifications. The aim of this study was to assess the eficacy and safety of low dose afatinib monotherapy in patients with EGFR mutation-positive NSCLC.

Methods

This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib in a dose of 20mg/day. The same dose was continued unless the tumor had grown. The primary endpoint (PE) was progression-free survival (PFS) The threshold median PFS was 9.2 months and the expected median PFS 13.8 months.

Results

From March 2017 through September 2018, 53 patients were enrolled from 21 institutions in Japan. The median age was 70 years (range, 37–85), and 28 patients (52.8%) were women. EGFR mutation subtypes included exon 19 deletion (56.6%) and L858R point mutation (43.4%). Most patients had a performance status of 0 or 1 (86.8%). As of the data cut-ofi date of March 2020, the median follow-up was 20.8 months. The median PFS, time to treatment failure and overall survival were 12.6 months (95% CI: 9.7–14.3), 18.6 months (95%CI: 16.0-21.2) and not reached. The PE was met. The objective response and the disease control were 66.6% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9). Adverse events (AEs) of grade 3 or higher occurred in 12 patients (22.6%) including diarrhea in 4 patients (7.5%) that was lower than that observed in phase III studies of afatinib using 40 mg. Eight of 19 patients (42.1%) had T790M resistant mutation in plasma and tissues. Afatinib plasma concentrations at 9 days after the start of administration had no correlations with clinical outcomes and AEs including diarrhea.

Conclusions

Low dose afatinib would be considered as one of standard therapy for EGFR mutation-positive NSCLCs because of promising clinical eficacy and good tolerability.

Legal entity responsible for the study

Thoracic Oncology Research Group.

Funding

Has not received any funding.

Disclosure

K. Kubota: Honoraria (self): Chugai Pharmaceutical, Taiho Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Bristol-Myers Squibb, kyowa-hakko Kirin, AstraZeneca, Ono Pharmaceutical; Research grant/Funding (institution): Ono Pharmaceutical, Nippon Boehringer Ingelheim. K. Naoki: Speaker Bureau/Expert testimony: Nippon Boehringer Ingelheim; Research grant/Funding (institution): Nippon Boehringer Ingelheim; Spouse/Financial dependant: Nippon Boehringer Ingelheim. A. Bessho: Honoraria (self): Nippon Boehringer Ingelheim. K. Minato: Research grant/Funding (institution): Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb. N. Seki: Honoraria (self): AstraZeneca, Nipppon Boehringer Ingelheim, Eli Lilly Japan, Daiichi Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical; Research grant/Funding (self): Nihon Medi-Physics, Nippon Boehringer Ingelheim; Research grant/Funding (institution): AstraZeneca. T. Tokito: Honoraria (self): AstraZeneca, Chugai Pharmaceutical, MSD. N. Furuya: Honoraria (self): Eli Lilly Japan, Chugai Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, Taiho Pharmaceutical, NipponBoehringer Ingelheim. H. Hayashi: Research grant/Funding (institution): Nippn Boehringer Ingelheim. H. Iihara: Research grant/Funding (institution): 19 飯原 大稔 附随研究 \"岐阜薬科大学 岐阜大学医学部附属病院” Nippon Boehringer Ingelheim. H. Okamoto: Research grant/Funding (institution): Takeda, MSD, Ono Pharmaceutical, AstraZeneca, Merck, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb, Eli Lilly Japan, Daiich Sankyo. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

402P - Efficacy and safety of sintilimab plus docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC) (ID 567)

Presentation Number
402P
Lecture Time
09:00 - 09:00
Speakers
  • Zhehai Wang (Jinan, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Immuno-checkpoint inhibitors (ICIs) has become standard second line therapy for advanced NSCLC patients (pts). However, early progression remained a major challenge with ICIs monotherapy. The synergetic effect of ICIs plus chemotherapy has been demonstrated in first line setting. Our study aims to explore if the combination of a PD-1 inhibitor with chemotherapy can provide additional clinical benefits in previously treated advanced NSCLC pts.

Methods

Advanced NSCLC pts who had failed standard platinum doublet without receiving any ICIs before would be enrolled in this single-arm phase II study. EGFR/ALK positive pts must be TKIs failure or intolerable. Eligible pts would receive docetaxel (75mg/m2, day 1) plus sintilimab (200mg, day 3) every 3 weeks for 4-6 cycles followed by sintilimab maintenance until disease progression, unacceptable toxicity, or up to 2 years. The primary end point is progression-free survival (PFS) per RECIST v1.1. Secondary end points included overall response rate (ORR), duration of response (DOR), overall survival, and safety.

Results

From 10/2019 to 4/2020, 28 pts were enrolled. Most were male (75%) and adenocarcinoma (85.7%). 21.4% pts had brain metastasis at baseline. Median follow-up was 5.1m (range 2.4-8.1) as of data cut-off (6/17/2020). 42.9% (12/28) pts were still on study treatment. PFS data was immature with only 35.7% (10/28) events. Estimated median PFS was 5.5m (95%CI 3.6-NE). Of the 25 evaluable pts, ORR is 24% (95%CI 9%, 45%), DCR is 92% (95%CI 74%, 99%). Median DOR was not reached (95% 1.28m, NA). Overall, 60.7% (17/28) pts had experienced treatment emergent adverse events (TEAEs), including 17.9% (5/28) grade 3-4 cases. No AEs led to treatment discontinuation or death. The most common TEAEs were leukopenia (50%), neutropenia (28.6%), alopecia (17.9%), lymphopenia (14.3%) and fatigue (14.3%).

Conclusions

This first report of a PD-1 inhibitor plus chemotherapy in advanced Chinese NSCLC pts who had failed first-line chemotherapy showed encouraging efficacy and tolerable safety profile. Enrollment is ongoing and more data will be presented.

Clinical trial identification

ChiCTR1900027634.

Legal entity responsible for the study

The authors.

Funding

Innovent Biologics, Inc.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

403P - Clinical profile, practice pattern and outcomes in ALK-positive lung cancer: Real-world data from India (ID 773)

Presentation Number
403P
Lecture Time
09:00 - 09:00
Speakers
  • Akhil Kapoor (Mumbai, Uttar Pradesh, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The use of ALK inhibitors is one of the success stories in the precision medicine for treating advanced ALK-positive non-small cell lung cancer (NSCLC). However, the developing countries have significant cost constraints in using ALK inhibitors. The primary objective of this study was to investigate the treatment patterns and outcomes in Indian ALK-positive NSCLC patients.

Methods

An audit of a prospectively collected database of advanced ALK-positive NSCLC patients treated from Jan 2013 to Dec 2017 was conducted. Patients were divided into those who received ALK inhibitor in first-line (including upfront strategy, or after a few chemotherapy cycles), or who did not receive ALK inhibitor in the first line. SPSS version 20.0 was used for statistical analysis.

Results

A total of 461 patients were available for analysis, 62.5% were males, median age 50 years (range 19-75) and 78.3% had ECOG PS 0-1. 169 (36.7%) patients were started on crizotinib upfront, 232 (50.3%) on chemotherapy, 12 (2.6%) received second/third-generation ALK inhibitors, and 22 (4.8%) patients were offered best supportive care. The main reasons for not starting crizotinib upfront included patients not willing to wait for the report (49.6%), financial constraints (21.3%), and symptomatic patients needing early initiation of therapy (13.3%). 78 (16.9%) patients were shifted to crizotinib after 1-2 cycles and 38 (8.2%) after 4-6 cycles of chemotherapy. The median progression-free survival on first-line therapy for the entire cohort was 14.1 months (m) (95% CI: 12.2-15.9), with a significant difference between patients receiving ALK inhibitor in first-line in any strategy vs. not in first-line [17.8 m (95% CI:14.9-20.8) vs. 5.9 m (95% CI:4.2-7.7), p<0.001). The median overall survival was 29.8 m (95% CI: 24.8-34.8), with 37.7 m (95% CI: 28.5-46.9) for ALK inhibitor in first-line vs. 20.2 m (95% CI: 15.6-24.7) for not in first-line (p<0.001). 295 (63.1%) received crizotinib completely free via various extramural support schemes.

Conclusions

A majority of our ALK-positive NSCLC patients were exposed to crizotinib through various support mechanisms. Those patients who could receive ALK inhibitors in the first-line had a significant survival advantage.

Clinical trial identification

CTRI/2013/01/003335.

Legal entity responsible for the study

Tata Memorial Hospital, Mumbai.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

404P - Financial toxicity in patients with advanced lung cancer treated with immunotherapy: Has it an effect on the clinical decision? (ID 981)

Presentation Number
404P
Lecture Time
09:00 - 09:00
Speakers
  • Jia-Hui Weng (Chengdu, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Patients with advanced lung cancer are considered to have a poor prognosis, and recent studies have shown that immunotherapy appears to be associated with improved prognosis and prolonged survival significantly compared with chemotherapy. However, immunotherapy may refer to a comparatively high medical cost and bring severe financial toxicity to patients. In the treatment course of patients with advanced lung cancer, much attention was paid to the safety and efficacy of medications, rather than financial toxicity, which may affect the prognosis and survival indeed. In that case, it is necessary to weigh the profit and the financial toxicity led by immunotherapy.

Methods

We performed a systematic search in Medline on the cost-effectiveness of immunotherapy in patients with advanced lung cancer, and 16 studies were included, consisting of 6 countries, We systematically reviewed the incremental cost for improved quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) in patients treated with immunotherapy with respect to different countries and different tumor proportion score (TPS) of programmed death receptor-1 ligand (PD-L1).

Results

We found that the willingness to pay (WTP) was not significantly associated with ICER among three western countries (P=0.354). Patients with TPS ≥50%, ≥20%, or ≥1% showed no significant differences in elevated QALYs (P=0.148) and ICER (P=0.263). The elevated QALYs (P=0.024) and ICER of Pembrolizumab were significantly higher than that of Atezolizumab (P=0.045), while there was no significant difference in the cost of elevated QALY between Pembrolizumab and Atezolizumab (P=0.747).

Conclusions

Patients with advanced lung cancer would get profit in the treatment of immunotherapy from different countries, while Pembrolizumab would be associated with a higher benefit and less financial toxicity when taking cost-effectiveness analysis into account. Thus, patients would get more in the immunotherapy when financial toxicity was taken into consideration, and it is necessary to integrate financial toxicity in the clinical decision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

405P - Promising efficacy as combination therapy of DFP-14323, protease inhibitor, with EGFR-TKI in patients with metastatic NSCLC harboring EGFR mutation (ID 243)

Presentation Number
405P
Lecture Time
09:00 - 09:00
Speakers
  • Hiroshige Yoshioka (Hirakata, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

DFP-14323(INN: Ubenimex) is protease inhibitor of aminopeptidase N (also called CD13), originated from Streptomyces olivoreticuli have been used for maintenance therapy of AML in Japan. Aminopeptidase is well known as one of prognostic factors for several cancer patients, including non-small-cell lung cancer (NSCLC). Otherwise, afatinib is one of the standard treatments in non-small-cell lung cancer (NSCLC) patients with EGFR mutation, but the toxicities often require dose adjustment. Recently, it is suggested that reducing afatinib doses can decrease treatment-related adverse events without affecting efficacy. We aimed to examine efficacy of DFP-14323 with low-dose afatinib by conducting phase II study in patients with metastatic NSCLC harboring EGFR mutation.

Methods

This study was a multi-center, single-arm, open-label phase II trial. Stage III/IV and treatment-naïve patients with common EGFR mutation-positive(L858R or 19del) NSCLC were treated with afatinib at a starting dose of 20 mg/day and DFP-14323 at a fixed dose of 10mg/day until disease progression or intolerable toxicity. Primary endpoint is disease control rate (DCR) defined by sum of CR, PR and SD (RECIST1.1) and secondary endpoints include progression-free survival, overall response rate and safety. A sample size of 26 patients was estimated based on α error of 0.05 (two sided), β error of 0.20, expected DCR 90% and threshold DCR 70% used the Simon’s two stage design.

Results

From July 2018 to March 2020, 26 patients were enrolled. Median age was 72 years (range, 53-82). Twenty-one patients (81%) were female, and 16 (62%) were never-smokers. Mutation subtypes were half Del-19 and half L858R. As of the data cut-off of June 2020, DCR was 100% (26/26) with 17 confirmed PRs. Grade 3 adverse events were observed in 5 (19.2%,1 diarrhea, 1 stomatitis, 2 paronychia, and 1 dermatitis), and all of these events were related with afatinib. No grade 4 or 5 adverse events were observed.

Conclusions

Combination of DFP-14323 and low-dose afatinib showed promising efficacy and good tolerability. We are planning a phase III study to evaluate this combination therapy after evaluation of PFS.

Clinical trial identification

UMIN 000033062.

Legal entity responsible for the study

Delta-Fly Pharma Inc.

Funding

Delta-Fly Pharma Inc.

Disclosure

H. Yoshioka: Honoraria (self), a clinical trial coordinator: Delta-Fly Pharma Inc.; Honoraria (self), lecturing: Boehringer Ingelheim. M. Mori, T. Yokoyama, K. Hirano: Honoraria (self), lecture: Boehringer Ingelheim. C-L. Huang: Honoraria (self), a clinical advisor: Delta-Fly Pharma Inc. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

406P - Anti-PD-1 versus anti-PD-L1 inhibitors in first-line therapy non-small-cell lung cancer: A systematic review and meta-analysis (ID 257)

Presentation Number
406P
Lecture Time
09:00 - 09:00
Speakers
  • Angelo B. Brito (Campinas, Brazil)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Due to the increasing number of trials with immune checkpoint inhibitors (ICI) in first line therapy of non–small cell lung cancer (NSCLC), we performed a systematic review and meta-analyses about the differences between anti PD-1 and PD-L1 in naïve-treatment NSCLC patients through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression free survival (PFS), overall response rate (ORR) and grade 3-5 adverse event (AE).

Methods

We included studies published until May 30 2020. Applicable terms, such as “lung cancer AND first line AND immunotherapy OR PD-1 OR PL-D1,” were used. Primary outcomes were OS, PFS, ORR and grade 3-5 AE. We used the random-effects model to generate pooled estimates for proportions. Meta-analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effect model. As there are no studies with direct analyzes between PD-1 and PD-L1 treatments, we carry out indirect data analyzes using the Excel spreadsheet. All analyses were performed by REVMAN version 5.0.

Results

Thirteen studies met our eligibility criteria, including 7673 patients (4077 cases in experimental and 3596 cases in control group). Six trials investigated ICI in monotherapy (four of them with anti-PD-1 and three with anti-PD-L1) and seven trials investigated ICI-chemotherapy combination; three used Pembrolizumabe and four used Atezolizumabe. Related to prognosis, in the ICI-chemotherapy combination group, anti-PD-1 were associated with better OS (P=0.02) and PFS (P=0.03) compared to anti-PD-L1. In monotherapy, there was no statistical difference between the use of anti-PD-1 and anti-PD-L1 for OS and PFS. Regarding ORR and toxicity, in the ICI-chemotherapy combination group, anti-PD-1 was associated with a trand better ORR (p=0.12) and less frequent grade 3-5 AE compared to the use of anti-PD-L1. In monotherapy, no statistical difference between the use of anti-PD-1 and anti-PD-L1 was observed.

Conclusions

Our study suggests that the combination of anti-PD-1 and chemotherapy is superior to anti-PD-L1 + chemotherapy in 1st line NSCLC therapy; in monotherapy both strategies appear to be similar.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

407P - Integrating histologic and genomic characteristics to predict tumour mutation burden of early-stage non-small cell lung cancer (ID 686)

Presentation Number
407P
Lecture Time
09:00 - 09:00
Speakers
  • Yuan Qiu (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tumor mutation burden (TMB) served as an effective biomarker predicting efficacy of mono-immunotherapy for non-small cell lung cancer (NSCLC). While, establishing a precise TMB predicting model is essential to monitor which populations are likely to respond to immunotherapy or prognosis and to maximize the benefits of treatment.

Methods

Available Formalin-fixed paraffin embedded tumor tissues were collected from 499 patients with NSCLC. Targeted sequencing of 636 cancer related genes were performed and TMB was calculated.

Results

Distribution of TMB was significantly (p < 0.001) correlated with sex, clinical features (pathological /histological subtype, pathological stage, lymph node metastasis and lympho-vascular invasion). It was also significantly (p < 0.001) associated with mutations in genes like TP53, EGFR, PIK3CA, KRAS, EPHA3, TSHZ3, FAT3, NAV3, KEAP1, NFE2L2, PTPRD, LRRK2, STK11, NF1, KMT2D and GRIN2A. No significant correlations were found between TMB and age, neuro-invasion (p=0.125), and tumor location (p= 0.696). Patients with KRAS p.G12 mutations and FAT3 missense mutations were associated (p< 0.001) with TMB. TP53 mutations also influence TMB distribution (P<0.001). TMB is reversely related to EGFR mutations (P<0.001) but is not differed by mutation types. According to multivariate logistic regression model, genomic parameters can effectively construct model predicting TMB, which may be improved by introducing clinical information.

Conclusions

Our study demonstrates genomic together with clinical features yielded a better reliable model predicting TMB-high status. A simplified model consisting of less than 20 genes and couples of clinical parameters sought to be useful to provide TMB status with less cost and waiting time.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D. Shao: Full/Part-time employment: BGI Genomics. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

408P - Integrated chemotherapy with EGFR receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring EGFR mutation (ID 755)

Presentation Number
408P
Lecture Time
09:00 - 09:00
Speakers
  • Julia Maevskaya (Moscow, Russian Federation)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lung cancer is the leading cause of cancer-related mortality worldwide. Chemotherapy and EGFR TKI combinations may be possible treatment options for patients with NSCLC and activating EGFR mutations. Many clinical trials have shown the potential benefits of these combinations.The addition of chemotherapy to first - and second - generation tyrosine kinase inhibitors significantly improved PFS compared with tyrosine kinase inhibitors monotherapy in treatment- naive patients with EGFR-mutated advanced NSCLC.We undertook the open prospective non-randomized multi -center study in a similar patient population.

Methods

We recruited patients with advanced NSCLC harboring EGFR mutations. Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The primary endpoint was progressive free survival (PFS) time.

Results

From May 2016 to May 2018, 54 patients with advanced (IIIB / IV stages) NSCLC, with activating mutation of the EGFR gene in exon 19 or 21, were included in the study. The objective response rate (ORR) was 55,5%. Serious adverse events were reported by 4 (7,4%) of 54 patients. 2-year PFS in all patients group included in the study at the time of the preliminary analysis was 38.9%, median PFS was 20,0 months (16.0–23,9CI 95%). Median overall survival was not reached.

Conclusions

Integrated chemotherapy with first - and second - generation tyrosine kinase inhibitors is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease, wich can help overcome acquired resistance to tyrosine kinase inhibitors. Tretment benefit of integrated chemotherapy compared with monotherapy of tyrosine kinase inhibitors 1-2 generations is obvious when comparing the results of our study with the data of randomized trials devoted to this problem.

Legal entity responsible for the study

K. Laktionov.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

409P - Effect of transdermal granisetron on prevention of nausea and vomiting during chemotherapy of lung cancer (ID 807)

Presentation Number
409P
Lecture Time
09:00 - 09:00
Speakers
  • Haifeng Qin (Beijing, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Chemotherapy is the basic treatments for lung cancer, and nausea and vomiting is one of the most common adverse event of chemotherapy, which decrease the life quality. As a result, how to prevent chemotherapy induced nausea and vomiting(CINV) is an important subject faced by oncologists. The granisetron transdermal delivery system (GTDS) has been developed to deliver granisetron continuously over 7 days to prevent CINV. Some previous cases receiving multiday highly emetogenic chemotherapy (HEC) regimens showed that the GTDS plus dexamethasone was not inferior to the GTDS plus dexamethasone and aprepitant. But there is no similar studies at home and abroad.

Methods

Our study prospectively assessed the non-inferiority of the GTDS plus dexamethasone to the GTDS plus dexamethasone and aprepitant in patients receiving multiday HEC. The primary endpoint was the proportion of patients with complete control of CINV from chemotherapy initiation until 24 h after final administration. The study has already enrolled 40 patients, 21 patients with two regimens, and 19 patients with three regimens before receiving multiday HEC.

Results

Between January 2019 and June 2020, 40 patients was recruited in the analysis. The GTDS plus dexamethasone group displayed non-inferiority to The GTDS plus dexamethasone and aprepitant group, complete control was achieved by 63.6% of patients in the two regimens group, and 65.4% in the three regimens group (P>0.05). Both treatments were well tolerated, the most common adverse events are manageable.

Conclusions

Current guidelines for the management of multiday HEC recommend three regimens therapy. Our study indicate that the two regimens therapy provides effective, well-tolerated control of multiday HEC. It offers a alternative route for delivering two regimens for up to 7 days that is as effective as three regimens.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

410P - Frequency and spectrum of primary resistance mechanism in Chinese ALK+ non-small cell lung cancer patients progressing on crizotinib: A multicenter study (ID 880)

Presentation Number
410P
Lecture Time
09:00 - 09:00
Speakers
  • Wen-xian Wang (Hangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Anaplastic lymphoma kinase (ALK) have been recognized as the most important predictor of response to crizotinib. However, 20-30% of patients harboring ALK fusion non-small-cell lung cancer patients show a poor response requiring investigation for underlying mechanisms.

Methods

We screened 3207 patients with NSCLC for ALK fusion. Among them, 92 patients received crizotinib treatment,and a total of 81 patients with stage IIIb-IV ALK+NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring resistance to crizotinib, including 43 formalin-fixed paraffin-embedded (FFPE) samples, 25 serum samples and 24 serous effusions. We used targeted NGS to detect genes status of patients.

Results

Among 92 patients treated with crizotinib, 76.09% (70/92) developed acquired resistance, and 11.96% (11/92) had primary resistance. Using the specimens at the baseline, there were 2 (18.18%) patients with BCL2L11 loss (BIM deletion polymorphism), 1 (9.09%) patient with PTEN mutation, 1 (9.09%) patient with PIK3CA mutation, 1 (9.09%) patient with CCND1 mutation, 1 (9.09%) patient with SMARCA4 mutation, 1 (9.09%) patient with CMTR1-ALK, 1 (9.09%) patient with EML4-ALK fusion (non A20), and 3 (27.27%) patients with unknown status.

Conclusions

BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), SMARCA4 mutations or EML4-ALK fusion (non A20) might contribute to molecular mechanisms of primary resistance to crizotinib in ALK+NSCLC.Further investigations are warranted to overcome these primary resistance.

Legal entity responsible for the study

Chun-wei Xu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

411P - Impact of pre-treatment AXL expression on osimertinib efficacy in patients with non-small cell lung cancer with EGFR mutation (ID 304)

Presentation Number
411P
Lecture Time
09:00 - 09:00
Speakers
  • Yoshihiko Taniguchi (Sakai, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, some patients show intrinsic resistance and an insufficient response to osimertinib. Increased expression of the anexelekto (AXL) protein in tumors is reported to be associated with poor prognosis in patients with several types of cancer. We previously reported the crucial role of the AXL pathway in the intrinsic resistance to EGFR-TKIs in EGFR-mutated NSCLC cells. Moreover, AXL overexpression in EGFR-mutated NSCLC specimens was negatively associated with the therapeutic efficacy of first- and second-generation EGFR-TKIs. However, the relationship between AXL expression in tumors and the therapeutic efficacy of osimertinib is still unclear.

Methods

We retrospectively enrolled 30 patients with advanced or relapsed NSCLC with EGFR-activating mutations from four institutions in Japan. All patients were administered osimertinib as the first-line treatment between August 2017 and March 2019.

Results

Twenty-two (73.3%) patients were female; 21 (70.0%) patients had never smoked. The median age of patients was 71.0 years (range, 44–88 years of age). The EGFR-activating mutations were deletion in exon 19 in 16 (53.3%) patients; L858R missense mutation in exon 21 in 12 (40.0%) patients; and other types in 2 (6.6%) patients. High (3+), intermediate (2+), low (1+), and no (0) pre-treatment expression of AXL in tumors was observed in 2 (6.7%), 4 (13.3%), 12 (40.0%), and 12 (40.0%) patients, respectively. The maximal tumor shrinkage rate following osimertinib treatment in the patients with AXL expression scores of 0 and 1+ was higher than that in patients with AXL expression scores of 2+ and 3+ (44.12% vs. 25.93%, p = 0.094).

Conclusions

Pre-treatment AXL expression in tumors may be a promising predictor of osimertinib treatment efficacy in patients with EGFR-mutated NSCLC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Yamada: Research grant/Funding (self): Pfizer Inc.; Research grant/Funding (self): Ono Pharmaceutical Co., Ltd; Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd; Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd. S. Atagi: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Ono; Honoraria (self), Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squib; Honoraria (self): Hisamitsu; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (institution): F. Hoffmann-La Roche. K. Takayama: Honoraria (self), Research grant/Funding (self): Chugai-Roche Co.; Research grant/Funding (self): Ono Pharmaceutical Co.; Honoraria (self): AstraZeneca Co.; Honoraria (self): MSD-Merck Co.; Honoraria (self): Eli Lilly Co.; Honoraria (self): Boehringer-Ingelheim Co.; Honoraria (self): Daiichi-Sankyo Co. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

412P - Treatment patterns and selection criteria for advanced non-small cell lung cancer (NSCLC) patients unfit for platinum-based first-line therapy: Results of the MOON-OSS observational trial (ID 509)

Presentation Number
412P
Lecture Time
09:00 - 09:00
Speakers
  • Andrea Camerini (Lido di Camaiore, (LU), Italy)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

A significant proportion of newly diagnosed advanced NSCLC patients does not receive a first-line platinum doublet due to unfavorable clinical characteristics.

Methods

We retrospectively collected data on 221 EGFR/ALK negative and PD-L1 <50% patients [median age 79 (range 56-92) years, M/F 165(74.6%)/56(25.4%), PS 0/1/≥2 23(10.4%)/94(42.5%)/103(47.1%), adenoK/squamous/large-cell/NOS 107(48.4%)/94(42.5%)/9(4.1%)/11(5%), median of 2 serious comorbidities] with stage IIIB-IV NSCLC treated with a first-line single agent. Clinicians were asked about the criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy.

Results

A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. The main clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), low PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%), oral metronomic vinorelbine (MetV 78.6%) and other (O 3.2%). Median time-to-progression (TTP) and overall survival (OS) of single agent treatments were Gem 4.5, Vin 4.5, MetV 5, O 5 months and Gem 9, Vin 9, MetV 10, O 10.5 months respectively. Overall grade 3-4 toxicities were lower with MetV (8%) than with Gem (13.6%), Vin (16.6%) and O (14.3%). Median TTP and OS without grade 3-4 toxicity were Gem 5, Vin 4.5, MetV 6.5, O 5.5 months and Gem 10, Vin 10, MetV 12, O 12 months respectively. Dose delays (Gem 41%, Vin 16.6%, MetV 13.8%, O 28.6%) and dose reductions (Gem 31.8%, Vin 33.3%, MetV 17.8%, O 28.6%) were less frequent with MetV.

Conclusions

We confirmed that up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 <50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70years), comorbidities and low (≥2) PS. An oral treatment was frequently proposed with MetV being the preferred alternative chosen by clinicians due to the excellent safety profile.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

413P - South Korean real-world treatment patterns in patients with EGFRm NSCLC (ID 637)

Presentation Number
413P
Lecture Time
09:00 - 09:00
Speakers
  • Jae Cheol Lee (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In Asia, ∼40% of patients (pts) with non-small cell lung cancer (NSCLC) are epidermal growth factor receptor-mutation (EGFRm) positive. T790M mutation occurs in ∼50% of pts who develop resistance to a first-/second-generation (1G/2G) EGFR-tyrosine kinase inhibitor (TKI). To investigate prevailing treatment patterns and T790M testing practices in pts with EGFRm locally advanced/metastatic NSCLC treated with first-line (1L) 1G/2G EGFR-TKI, real-world (RW) data were obtained from pts in South Korea.

Methods

Retrospective, non-interventional medical record review of pts with EGFRm NSCLC treated with 1L 1G/2G EGFR-TKIs in routine practice settings between 1 Jan 2015–31 Dec 2017 (follow up: end 2019). Study endpoints: demographic/disease characteristics, 1L EGFR-TKI therapy selection, T790M mutation testing and second-line (2L) therapy selection.

Results

235 pts were included: median age 70 (40–93) years, 63% female, and 64% never smoked. At initial NSCLC diagnosis, 89% of pts had metastatic disease, 63% had an ECOG PS score of 0/1; 57% were ex19del positive. 1L 1G/2G EGFR-TKI therapy: 45% afatinib; 43% gefitinib; 13% erlotinib. 164/235 pts (70%) progressed on 1L therapy; median treatment duration of 10.3 months (mo; range: 0.1–37.2). 71/235 pts (30%) did not progress: 37 (16%) remained on 1L therapy and 34 (14%) discontinued 1L therapy before end of follow-up. 22/235 (9%) died during/after 1L therapy without receiving 2L therapy. Following progression, 68% (n=111/164) were tested for T790M, 43% (n=48/111) were T790M positive; 88% (n=42/48) of those received osimertinib. Overall, 120/164 (73%) received 2L therapy – mainly pemetrexed (n=49; 41%).

Conclusions

In this study, of pts who progressed on 1L 1G/2G EGFR-TKI, 27% did not receive 2L therapy, while only 68% were T790M tested; 88% of positive pts received osimertinib. Suboptimal rates of mutation testing and use of recommended 2L therapies may reflect the fact osimertinib was not reimbursed in South Korea until Dec 2017.

Editorial acknowledgement

Louise Prince, PhD of Ashfield Healthcare Communications, part of UDG Healthcare plc, who provided medical writing support funded by AstraZeneca, Cambridge, UK, the manufacturer of osimertinib, in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y-C. Kim: Honoraria (institution), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim. K. Davis: Research grant/Funding (institution), Full/Part-time employment, Employee of RTI Health Solutions, which has received contract research funding from AstraZeneca for my participation in the conduct of the currently submitted study/abstract: RTI Health Solutions; Research grant/Funding (self): Novartis; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Vertex; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): Eisai. S.P. Nagar: Full/Part-time employment: RTI Health Solutions. W. Sawyer: Full/Part-time employment, I am an independent statistical contractor working for AstraZeneca. N. Yu: Full/Part-time employment: AstraZeneca. A. Taylor: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

414P - Incidence and characteristics of lung cancer diagnosed after kidney transplantation at the National Kidney and Transplant Institute (ID 819)

Presentation Number
414P
Lecture Time
09:00 - 09:00
Speakers
  • Adeline C. Gonzales (Quezon City, Philippines)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Kidney transplant recipients have increased risk of malignancy. They are also maintained on immunosuppressive agents which make them prone to infection and makes it more complicated when dealing with cancer in this population. Lung cancer, likewise, is the leading cause of mortality among all cancer types in the general population. It is thus the purpose of this paper to determine the incidence of lung cancer in post kidney transplant patients and provide information on how these patients are managed, as well as describe outcomes in each.

Methods

A retrospective review of medical records of patients with lung cancer after kidney transplantation at National Kidney and Transplant Institute from January 1983 to December 2018. Incidence and clinicodemographic characteristics were determined. Kidney function after cancer diagnosis were investigated. Overall survival and progression free survival were determined in Kaplan-Meier curves.

Results

Only five (n=5) or 0.076% of 6,580 kidney transplant recipients developed lung cancer. Eighty percent (80%) were diagnosed at stage IV. All were diagnosed at symptom onset, and no screening chest CT were done post-transplant. One patient diagnosed at an early stage underwent surgical lobectomy while 2 patients diagnosed at stage IV had undergone chemotherapy. Two patients (40%) had creatinine clearance lower than baseline during the course of lung cancer disease, and one patient (20%) had acute rejection. Median overall survival is 3.4 months (95% CI 0.87 - 12.47).

Conclusions

Lung cancer occurred in 0.076% of kidney transplant recipients, and most are in advanced stage. Additional studies are needed to determine association of systemic treatment and survival, as well as adverse reactions of treatment particularly in kidney transplant recipients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

415P - Real-world fusion landscape of RET gene fusions and its response to cabozantinib in Chinese non-small cell lung cancer (NSCLC) using next generation sequencing (ID 886)

Presentation Number
415P
Lecture Time
09:00 - 09:00
Speakers
  • Chunwei Xu (Fuzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

RET fusion is one of the rare driver genes in lung cancer and thyroid carcinoma and and RET-directed therapies have shown promising results in this unique population. The aim of this study was to investigate the efficacy of cabozantinib in patients with advanced RET fusion NSCLC.

Methods

A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2019. To determine the frequency of the RET fusions in NSCLC and other tumors, we analyzed data from 3046 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient.

Results

Of this entire cohort, 61 (2.00%) patients were identified with a RET fusion, including KIF5B-RET (40), CCDC6-RET (16), NCOA4-RET (1), ANK3-RET (1), ERC1-RET (1), RYFY2-RET (1) and CSGALNACT2-RET (1). 8 cases coexist with EGFR mutations, were all used EGFR-TKIs treatment. For treatments, 14.75% (9/61) patients chose cabozantinib, other patients chose chemotherapy or chemoradiotherapy, and case examples of advanced RET fusion driven NSCLC patients responding to cabozantinib were actively being sought thru our database.

Conclusions

Patients with advanced RET fusion NSCLC showed a relatively good outcome of cabozantinib with relatively large side effects, which strengthen the need for effective RET-targeted drugs in clinical practice.

Legal entity responsible for the study

Chun-wei Xu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

416P - A single institute study evaluating the additional benefit of blood NGS testing over conventional molecular testing in metastatic adenocarcinoma lung (ID 977)

Presentation Number
416P
Lecture Time
09:00 - 09:00
Speakers
  • Rajashree Ashwath (Bangalore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Identification of molecular subgroups has revolutionized the treatment of metastatic adenocarcinoma lung.Practice in India is to test for EGFR hotspot mutations by PCR, ALK by IHC and ROS1 by FISH (conventional testing).Tissue NGS (next generation sequencing) testing is increasing; but availability of adequate tissue is a problem.Aim of our study was to evaluate the added benefit of blood NGS testing in patients who were negative by conventional molecular testing.

Methods

This was a retrospective analysis of patients with metastatic lung cancer, who presented at Manipal hospital, Bangalore, Jan 2019 and May 2020.

Results

108 patients, 35-75 years, were analyzed. 78 (72%) men, 30(28%) women. 87 (80.6%) had adeno and 21 (19.4%) had squamous cell carcinoma. All adenocarcinoma patients were tested on tumor tissue for EGFR hotspot mutations by PCR, ALK by IHC and ROS1 by FISH. Molecular alterations by conventional testing were found in 34 (39%) patients and 53(61%) were negative. Out of these 34, 29 (33%) had EGFR, 3 (3.1%) had ALK and 2 (2.4%) had ROS1 alterations. We further evaluated the conventionally tested negative patients to blood NGS testing (liquid biopsy). Only 20 (37%) out of the 53 conventionally tested negative patients were subjected to blood NGS testing due to logistic reasons. We found 14 (70%) out of 20 had detectable mutation on blood NGS. Out of the 14, we picked up 6(42%) EGFR (3 common, 3 uncommon), 1 (7 %) ALK, 1 (7 %) ROS1, 1 (7 %) MET exon 14 skip, 2 ( 14%) HER 2 and 3 (21 %) RAS mutations (G12C). We treated 10(50%) out of 20 subjects: 5 EGFR mutation patients with geftinib/afatinib/ osimertinib, 1 ALK with crizotinib, 1 ROS with crizotinib, 1 MET with Capmatinib, and 2 HER2 with Afatinib.

Conclusions

Findings of our study proves patients who are negative by conventional testing should be further evaluated with blood NGS testing. In our study, inspite of limited testing, we were able to detect additional 14 patients with driver mutations by doing blood NGS testing, thus increasing our mutation detection from 39% to 55%.Advantage of blood NGS testing is ease of sample collection, faster turnaround time, that it is able to overcome the common problem of inadequate tissue in lung cancer.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

417P - Efficacy and safety of lorlatinib in subsequent lines of therapy in ALK and ROS1 positive lung cancer (ID 1008)

Presentation Number
417P
Lecture Time
09:00 - 09:00
Speakers
  • Amit Kumar (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Lung Cancer is a disease with diversity. ALK and ROS1 positive lung cancer constitute one end of the spectrum with a favorable outcome. Lorlatinib has been approved in November,2018 for disease progressing on first and second line ALK inhibitor. We are presenting the outcome data of Lorlatinib in subsequent lines of therapy.

Methods

We retrospectively collected data from Medical Oncology department for ALK and ROS1 positive patients who received lorlatinib post progression on initial therapy.The demographic details, histology, prior treatment, clinical and radiological response, date of disease progression, date of death and toxicity data were collected.We included patients who were started on treatment on 31st December,2019 or earlier.

Results

There were 41 patients in the database who received Lorlatinib.The median age was 47 years (range 23-68 ), with 54% being male. Forty one percent patients have comorbidities; the most common being hypertension and diabetes and 81% patients were of ECOG-PS-1. Three patients were ROS1 positive. Twenty four patients (59%) received two prior TKIs. The most common site of metastasis before starting Lorlatinib were brain(59%) and bone(57%).All patient except one received prior WBRT with 4 being irradiated twice. The median follow up period was 16 months (95% CI: 14.4-17.5).Seventy three percent showed clinical response to therapy with median PFS and OS of 16 months (95% CI 14.0-18.2) and 23 months (95% CI 14.6-31.3) respectively. The most common site of progression was lung (67%) and pleural effusion(33%). Ten out of eighteen patient who progressed received subsequent therapy. The most common grade 3 and above toxicity were hypercholesterolemia and hypertriglyceridemia. Three patients underwent dose reduction.

Previous lines of therapy n (%)
1 5 (12.2)
2 17 (41.5)
3 11 (26.8)
>4 8 (19.5)
>1 TKI 24 (58.5)
Response
Complete response 1 (2.4)
Partial response 8 (19.5)
Stable disease 20 (48.8)
Progressive disease 5 (12.2)
Non evaluable 7 (17)
Clinical benefit
Yes 30 (73)
No 11 (27)
.

Conclusions

Lorlatinib seems to be a potent drug in subsequent lines with tolerable side effects.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Noronha: Research grant/Funding (institution): Dr. Reddy’s Laboratories; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Sanofi Aventis. K. Prabhash: Research grant/Funding (institution): Biocon Ltd; Research grant/Funding (institution): Dr. Reddy’s Laboratories; Research grant/Funding (institution): Fresenius Kabi India Pvt. Ltd.; Research grant/Funding (institution): Alkem Laboratories; Research grant/Funding (institution): Natco Pharma Ltd.; Research grant/Funding (institution): BDR Pharmaceutics Intl Pvt. Ltd.; Research grant/Funding (institution): Roche Holding AG. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

418P - All EGFR mutations are (not) created equal: Focus on uncommon EGFR mutations (ID 995)

Presentation Number
418P
Lecture Time
09:00 - 09:00
Speakers
  • Ullas Batra (New Delhi, Rohini, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The treatment of NSCLC has changed drastically in the last decade since the discovery of biomarkers like EGFR, ALK, ROS etc. Most common EGFR mutations in NSCLC include del19 and exon 21 L858R mutations. However, approximately 10% of NSCLC patients have uncommon EGFR mutations (complex indels undetected by single gene testing, missense mutations involving G719, L861, & S768 codons, and exon 20 insertions) which do not respond as well to TKIs. Thus, it is very important to understand type of EGFR mutations in clinical practice. This retrospective study reviews prevalence of these mutations in an Indian NSCLC cohort along with the clinicopathologic characteristics.

Methods

A total of 470 EGFR mutated NSCLC were analyzed. Of these, cases harboring uncommon EGFR mutations (n=49), were reviewed retrospectively, for clinicopathologic features. This study was approved by ethics committee of the institute.

Results

Of the 470 cases, 49 (10.42%) were found to have uncommon EGFR mutations. The median age was 66 years (35-87years). Almost equal sex predilection with 25 (51%) males and 24 (49%) females. Among these, 39 (79.6%) were never smokers, 7 (14.3%) smokers. Intrathoracic metastases in form of lung-lung spread were noted in 20 patients (40.8%); lung-pleura in 38 (77.6%) patients. Extrathoracic metastases noted include brain (n=18, 36.7%), liver (n=14, 28.6%), bone (n=25, 51%), &adrenals (n=4, 8.2%). Thirteen cases had dual mutations in EGFR including L861Q and G719X in 3 patients, G719X and S768I in 1 patient, L858R and S768I in 1 patient, del19 and L8585R in 1 patient and additional T790M with del 19 and L858R in 4 and 2 patients respectively. The mutation profile of patients with single mutations included 4 cases of L861, 5 cases of S768,8 cases of G719, 1 case of exon 18 insertion and 14 cases of exon 20 insertion. Patients with L861Q were males (p<0.047) and never smokers (p<0.018). Exon 20 insertions were more common in females (p<0.024). Nine patients received TKI treatment; Seven were treated with afatinib and two with osimertinib (one patient had T790M mutation, the other had S768I mutation).

Conclusions

Rare and dual EGFR mutations are a heterogeneous group with distinct clinical features. This study highlights the same in an Indian cohort of EGFR mutated NSCLC.

Legal entity responsible for the study

Ullas Batra.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

419P - Surgical treatment of malignant tumours and metastatic lesions of the chest wall (ID 548)

Presentation Number
419P
Lecture Time
09:00 - 09:00
Speakers
  • Zhanat U. Pyssanova (Almaty, Kazakhstan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Tumors of the chest wall are relatively rare. Malignant tumors of the chest wall make up 4% of the structure of cancer and 1-2% of all primary tumors. Malignant tumors of the ribs and sternum made up 13% of the number of patients with bone tumors. The main treatment for chest wall tumors is surgical treatment. Unlike primary, metastatic bone tumors occur 2-4 times more often.

Methods

From 2010 to 2019, in KazIOR provide operations for 78 patients with chest wall tumors, in which 60(76.9%) malignant bone tumors (chondrosarcoma 26(33.3%) and osteogenic sarcoma 34(43.6%), 2(2.6%) metastatic bone lesions, 16(20.5%) soft tissue tumors. The average age was 46.4years, the ratio of men and women 1: 1. 16(20.5%) patients underwent resection of the sternum (manubrium 2(2.6%), body 5(6.4%), xiphoid process 3(3.9%), middle third of the sternum 2(2.6%), the sternum and clavicle 2(2.6%), the xiphoid process of the sternum+costal arch of both sides+diaphragm and peritoneum in 1(1.2%) patient, middle third of the sternum+clavicle+3 ribs 1(1.2%)) and 62(79.5%) resection of the ribs (1 rib 14(17.9%), 2 ribs 12(15.5%), 3 ribs 3(3.9%), 4 ribs 3(3.9%), 5 ribs 1(1.2%), costal arch 1(1.2%), 28(35.9%) patients combined resection of ribs with nearby bones of the chest wall, various structures of the mediastinum and visceral organs.

Results

After resection of 3 ribs or more along the anterolateral surface and total or subtotal resection of the sternum 39(50%) patients underwent reconstructive plastic surgery. In 25(32%) cases used prolene mesh, in 2(2.6%) a displaced skin-fat flap, in 2(2.6%) a thoracodorsal flap (TDL), in 2(2.6%) a greater omentum and in 8(10.2%) combined plasty (prolene mesh+rectoabdominal flap in 2(2.6%) patients, prolene mesh+displaced pectoral flap in 4(5.1%), prolene mesh+TDL in 1(1.2%), prolene mesh + skin-fatty flap in 1(1.2%).

Conclusions

Due to the radical removal of the tumor in combination with the reconstruction of postoperative extensive defects of the chest wall, the quality of life of patients is improved and good functional results are achieved - ease of construction and at the same time the required rigidity of the frame. Despite a significant amount of experimental work research in this area is ongoing.

Legal entity responsible for the study

Kazakh Reserch Institute of Oncology & Radiology (KazIOR).

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

420TiP - UpSwinG: Real-world study of TKI activity in patients with EGFR mutation-positive (EGFRm+) NSCLC with uncommon mutations, and sequencing of afatinib followed by osimertinib (ID 529)

Presentation Number
420TiP
Lecture Time
09:00 - 09:00
Speakers
  • Satoru Miura (Niigata, Japan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

EGFR TKIs are established as an effective treatment for patients with EGFRm+ NSCLC harboring common mutations (Del19 or L858R). However, 7% to 23% of NSCLC tumors harbor uncommon EGFR mutations, where EGFR TKI efficacy is less established. Up to 75% of patients treated with afatinib develop T790M resistance. Second-line osimertinib is highly effective in these patients. In the GioTag study, sequential afatinib and osimertinib was associated with encouraging outcomes (median TTF and OS: 28.1 and 41.3 months, respectively) in 203 patients who developed T790M mutations after first-line therapy in a real-world setting.

Trial design

This real-world, non-interventional, global, multi-center study (UpSwinG; NCT04179890) will enroll ∼400 patients with EGFR TKI-naïve advanced (stage IIIB/IV) EGFRm+ NSCLC treated with EGFR TKIs across ∼65 study centers in ≤11 countries. Pre-existing data will be retrospectively collected from medical records (paper or electronic); selection bias will be minimized where possible, including by selecting only consecutive patients meeting each of the inclusion criteria and none of the exclusion criteria. The study comprises two cohorts (∼200 patients each). Cohort 1 will include patients with tumors harboring uncommon or compound EGFR mutations who received first- or second-line EGFR TKI treatment. Cohort 2 will include patients with common EGFR mutations who progressed on first-line afatinib, tested positive for T790M and were subsequently treated with second-line osimertinib (40 or 80 mg/day). Key exclusion criteria include prior participation in other EGFRm+ NSCLC studies and patients with active brain metastases. Across both cohorts, the primary objective will be time on treatment, defined from the start of EGFR TKI treatment until the end of EGFR TKI treatment or death by any cause in cohort 1, and from the start of first-line until the end of second-line treatment or death by any cause in cohort 2. Secondary objectives include overall response rate, overall survival, and time on second-line treatment (in cohort 1). Thus far, 256 patients have been recruited: 206 in cohort 1, and 50 in cohort 2.

Clinical trial identification

NCT04179890.

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Steven Kirkham, of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the preparation of this abstract

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

S. Miura: Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Taiho Pharma; Speaker Bureau/Expert testimony: Ono Pharma; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Abbvie; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin. A. Märten: Full/Part-time employment: Boehringer Ingelheim. S. Popat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AZ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Paradox; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Ariad.

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e-Poster Display Session (ID 87) Poster Display

General Interest (ID 1160)

Lecture Time
09:00 - 09:00
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00
e-Poster Display Session (ID 87) Poster Display

421P - A multicenter, randomized, double-blind, placebo (PBO)-controlled, phase III trial of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in China (ID 365)

Presentation Number
421P
Lecture Time
09:00 - 09:00
Speakers
  • Ming Gao (Tianjin, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

LEN is a multikinase inhibitor of VEGFRs 1–3, FGFRs 1–4, PDGFRα, RET, and KIT that resulted in significantly prolonged progression-free survival (PFS) compared with PBO in pts with RR-DTC in a phase III study (SELECT). However, SELECT did not include pts from China. As data in Chinese pts are required for approval of LEN for RR-DTC in China, we conducted a phase III study of RR-DTC treated with LEN vs PBO in Chinese pts.

Methods

This randomized, multicenter, double-blind, PBO-controlled study enrolled pts aged ≥18 years with RR-DTC and confirmed disease progression in the past 12 months. Pts were stratified by tumor subtype (papillary or follicular), number of prior VEGF/VEGFR-targeted therapies (0 or 1), and age (≤65 years or >65 years). LEN starting dose was 24 mg/day. The primary endpoint was PFS by independent imaging review based on RECIST v1.1. A one-sided significance level of 0.01 was utilized in the planned interim analysis. Secondary endpoints included overall response rate (ORR), overall survival, and safety.

Results

Overall, 151 Chinese pts (median age, 60 years; 52% men) were randomized 2:1 (LEN, n = 103; PBO, n = 48). At the recommendation of the Independent Data Monitoring Committee at the time of the interim analysis, the randomization phase of this study was stopped early because of positive efficacy and we conducted the primary analysis using the interim analysis cutoff date. In the LEN and PBO arms, the median durations of follow-up were 14.8 and 15.6 months, respectively. PFS was significantly improved with LEN (median 23.9 months; 95% CI 12.9–not estimable) vs PBO (median 3.7 months; 95% CI 1.9–5.6) (hazard ratio = 0.16, 95% CI 0.10–0.26; P < 0.0001 [logrank]). ORR was 69.9% with LEN and 0% with PBO. The most common treatment-related grade ≥3 adverse events (LEN, PBO) were hypertension (62.1%, 4.2%), proteinuria (23.3%, 0%), and palmar-plantar erythrodysesthesia syndrome (9.7%, 0%).

Conclusions

LEN significantly prolonged PFS compared with PBO in Chinese pts with RR-DTC, similar to the global phase III SELECT results. There were no new or unexpected toxicities with LEN in Chinese pts with RR-DTC.

Clinical trial identification

NCT02966093.

Editorial acknowledgement

Medical writing was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Eisai Co., Ltd., Tokyo, Japan, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Disclosure

T. Kubota, T. Suzuki, H. Ikezawa: Full/Part-time employment: Eisai Co., Ltd. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

422P - Response rate and time to progression after first line chemotherapy with cisplatin and adriamycin in patients with metastatic osteosarcoma at presentation (ID 410)

Presentation Number
422P
Lecture Time
09:00 - 09:00
Speakers
  • Sivasubramaniam Kumaravelu (Chennai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Metastatic osteosarcoma at presentation forms 10 to 20% of total osteosarcomas diagnosed. They have a very poor prognosis compared to non-metastatic subset. Patients with resectable metastasis have a better DFS and OS compared to unresectable metastatic disease at presentation. This study was done to find the response rate to first line cisplatin and adriamycin combination chemotherapy to upfront metastatic osteosarcoma patients and time to progression after first line chemotherapy. Secondary objective was to find the overall survival.

Methods

Patients diagnosed with osteosarcoma at madras medical college were identified from the database for a period of 5.5 years from January 2013 to June 2018. From that patients who had metastasis at presentation were further sorted out and taken for analysis.

Results

77 patients were diagnosed to have osteosarcoma during the 5.5year period. Among them 36 patients had metastatic disease at presentation. 28 patients were male (77.8%) and 8 patients were female (22.2%). Median age of the patients was 19.5 years. 23 patients had ECOG PS 2 (63.9%) and 12 had ECOG PS 1 (33.3%) and 1 had ECOG PS 3 (2.8%). Tibia and femur were the most common primary site (75%). 5 patients had resectable lung metastasis and underwent pulmonary metastasectomy and were excluded from analysis and 1 patient was on palliative care only. Among remaining 30 patients, 27 patients had multiple lung metastasis (90%) and 3 patients had bone metastasis (10%). 30 patients received 6 cycles of chemotherapy with adriamycin 25mg/m2 on d1-d3 and cisplatin 100mg/m2 on d1 repeated every 21 days except 3 who progressed during chemotherapy. 17 patients (56.7%) had grade 1-2 vomiting. No one developed any acute cardiotoxicity. No treatment related death occurred. At the end of 6 cycles, 22 patients (73.3%) had partial response and 5 patients (16.7%) had stable disease and 3 patients (10%) had progressive disease. Median time to progression was 11.5 months. 2year OS was 73.3%.

Conclusions

This platinum doublet is a reasonable option for these patients as most of them are young.

Legal entity responsible for the study

Sivasubramaniam Kumaravelu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

423P - Positive lymph node and thicker Breslow are associated with poor prognosis of high-risk resected melanomas (ID 421)

Presentation Number
423P
Lecture Time
09:00 - 09:00
Speakers
  • Roby Cahyono (Yogyakarta, Indonesia)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Nodular, acral, and mucosal melanomas that represent non-cumulative sun damage lesions account for more than 60% of melanomas in Asia but comprise only 4% in Caucasians. The distinct spectrum of manifestations might influence the clinical course and outcomes. Factors associated with the prognosis of high-risk resected melanomas from Indonesia have not yet been previously reported.

Methods

Demographic, clinical, pathological characteristics of 82 melanoma patients who underwent complete resection in 2014-2019 were analyzed.

Results

Nodular melanoma (NM), mucosal melanoma (MM), and acral lentiginous melanoma (ALM) made up of 42.7% (n=35), 42.7% (n=35), and 14.2% (n=12) of cases, respectively. Most patients were diagnosed at advanced stages (76.8%, n=63 at Stage III-IV). For cutaneous melanomas, 89% (N=42) patients were found with Breslow’s tumor thickness more than 4 mm, 51% (N=24) with ulceration, 93% (N=43) with diameter more than 6 mm, 59% (N=28) with lymphovascular invasion, and 74% (N=35) with regional lymph node infiltration. In mucosal melanomas, 14.5% (N=5) were diagnosed with regional spread to lymph nodes and 77% cases (N=27) were found with regional infiltration beyond mucosa. Regional lymph node spread was associated with shorter overall survival (median survivals were 17 vs 23.4 months, Mantel-Cox test p=0.049). Patients diagnosed at T4 were also associated with poor overall survival (median survivals were 23 vs 32 months, Mantel-Cox test p=0.047).

Conclusions

Most melanoma patients in Indonesia were found as a higher risk for recurrence after the initial complete resection. Regional lymph node infiltration and thicker tumor (T4) were associated with poor prognosis. Early detection and advancement of treatment strategy are required to improve the survivals of melanoma patients in Indonesia.

Legal entity responsible for the study

Sumadi Lukman Anwar.

Funding

Universitas Gadjah Mada.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

424P - Hippocampus sparing in volumetric modulated arc therapy (VMAT) for brain tumour radiotherapy treatment (ID 422)

Presentation Number
424P
Lecture Time
09:00 - 09:00
Speakers
  • Eva Yi Wah Cheung (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Radiotherapy is a primary or an adjuvant treatment for most brain tumor patients for better tumors control and prolong survival [1]. However, cranial irradiation may cause damages to hippocampus (plural: hippocampi), which may induce dementia after they recovered from the disease [2]. To minimise radiation dose to hippocampus becomes a new trend in radiation therapy [3], [4]. This study is to investigate whether traditional coplanar VMAT (CO-VMAT) or proposed non-coplanar VMAT (NC-VMAT) is dosimetrically superior for brain tumor radiotherapy treatment in view of hippocampus sparing.

Methods

Both CO-VMAT plan and NC-VMAT plan were generated for 16 brain tumor patients (Glioblastoma: 11, Meningioma: 5) using Varian Eclipse planning system version 15.6. The prescription was to give 54 Gy to PTV in 30 fractions. Dose constraints applied for plan optimization were benchmarked against Radiation Therapy Oncology Group (RTOG). In the CO-VMAT plans, there were 1 full arc (179°-181°) and 2 half arcs. The couch angle for all arcs were 0°. For cases with PTV located at the left side of the brain, the gantry angle for the 2 half arcs were set from 0°to 179° and 179° to 0°. While for cases with PTV on the right side of the brain, the gantry angle of the 2 half arcs were set from 0° to 181°and 181°to 0°. In the NC-VMAT plans, all setting were the same as CO-VMAT plans, except that the couch angle for the 2 half arcs was at 315° for PTV located at the left side of the brain, and 45° for PTV located on the right side of the brain.

Results

Homogeneity index, conformation number, dose to other organs at risk and ipsilateral hippocampus were similar in CO-VMAT and NC-VMAT plans. The maximum dose (D-MaxCH) received by contralateral hippocampus in NC-VMAT is 4Gy lower (p=0.049) than that of the CO-VMAT. The dose received by 40 % of the contralateral hippocampus (D40%CH) in NC-VMAT is 1.46Gy (p=0.003) lower than that of the CO-VMAT. The mean D-MaxCH and mean D40%CH were reduced by 23% and 23.5% respectively in NC-VMAT plans when compared with CO-VMAT.

Conclusions

The NC-VMAT is able to minimize radiation dose to contralateral hippocampus while maintaining good plan quality. The NC-VMAT approach may help to consolidate the development of a new standard of care for brain tumor patients.

Legal entity responsible for the study

Tung Wah College.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

425P - The impact of obesity on treatment outcomes in patients with solid tumour malignancies treated with first-line (1L) immuno-oncology (IO) agents (ID 494)

Presentation Number
425P
Lecture Time
09:00 - 09:00
Speakers
  • Chun Loo Gan (Calgary, Canada)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The obesity survival paradox refers to the unexpected association of obesity with improved cancer survival outcomes. This phenomenon has been previously reported in IO treated solid tumor malignancies. We aimed to assess the impact of obesity on clinical outcomes in patients with advanced solid tumors treated with contemporary 1L IO based therapy.

Methods

Using the International Metastatic Renal Cell Carcinoma (RCC) Database Consortium and Alberta Immunotherapy Database, patients with advanced RCC, non-small cell lung cancer (NSCLC) or melanoma treated with 1L PD-(L)1 inhibition +/- tyrosine kinase inhibitor (RCC), chemotherapy (NSCLC) or CTLA-4 inhibitor (RCC/Melanoma) were included. As has been done in other analyses in the obesity paradox field, a comparison with obese (BMI ≥ 30.0 kg/m2) vs. normal weight (BMI 18.5-24.9 kg/m2) individuals was performed. Underweight (BMI < 18.5 kg/m2) patients (to avoid cachexia as a confounder) and overweight (BMI 25.0-29.9 kg/m2) patients (to not dilute the effect of obesity) were excluded. Objective response rate (ORR), time to treatment failure (TTF) and overall survival (OS) were calculated.

Results

Of 1067 patients, 30% and 33% of patients were found to be obese and normal weight, respectively. There were more males in obese vs. normal weight patients (66% vs. 55%, p<0.01). In NSCLC, PDL-1 expression was not different (p=0.39); and in RCC, there were less IMDC intermediate/poor risk patients among obese vs. normal weight patients (81% vs. 87%, p <0.01). In melanoma, there was no difference in BRAF status (p=0.68), LDH level (p=0.32), or metastatic burden (p=0.81) between obese vs. overweight patients. Overall, obese patients experienced a superior OS compared to normal weight patients (Table). Changing the BMI threshold to compare BMI ≥ 25 kg/m2 vs. normal weight yielded a similar result (median OS of 31.6 vs. 21.8 mons, p <0.01, respectively). Subgroup analysis by tumor type showed that the observed benefit was primarily driven by NSCLC. We were unable to detect a significant difference in OS among obese vs. normal weight patients with RCC or melanoma. In the RCC subgroup, there was a higher response rate in obese patients compared to normal weight patients.

Clinical outcomes of patients with obesity vs normal weight

Clinical outcome Obesity Normal weight P-value
Overall cohort (N=669) N=316 N=353 -
ORR %, (n/n) 47% (125/265) 40% (107/271) 0.07
mTTF (mon) (95% CI) 6.0 (4.9-7.5) 4.8 (3.5-7.4) 0.41
mOS (mon) (95% CI) 32.2 (25.1-53.4) 21.8 (16.3-28.1)) 0.01
RCC (N=250) N=140 N=110 -
ORR 47% (58/123) 31% (28/90) 0.02
mTTF 7.6 (6.0-11.0) 6.8 (3.0-9.6) 0.86
mOS 47.8 (29.6-57.8) 30.9 (20.0-41.4) 0.41
NSCLC (N=238) N=84 N=154 -
ORR 35% (24/69) 34% (38/112) 0.90
mTTF 5.8 (3.6-11.3) 3.7 (2.7-4.9) 0.20
mOS 24.8 (18.5-28.3) 8.6 (6.4-20.4) 0.02
Melanoma (N=181) N=92 N=89 -
ORR 59% (43/73) 59% (41/69) 0.95
mTTF 4.6 (3.2-5.7) 6.9 (2.9-10.8) 0.48
mOS 22.2 (13.0-NR) 26.9 (18.9-NR) 0.62

mTTF=median TTF, mOS=median OS

Conclusions

The obesity paradox exists in NSCLC. We are unable to demonstrate this finding in RCC, although the response rate was higher in obese patients. In melanoma, there was no difference in outcomes among obese vs. normal weight patients. The effect of obesity on treatment outcomes may be dependent on primary tumor type.

Legal entity responsible for the study

Daniel Y.C. Heng.

Funding

Has not received any funding.

Disclosure

J.C. Wells: Travel/Accommodation/Expenses: Pfizer. S.K. Pal: Advisory/Consultancy: Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol-Myers Squibb, Astellas Pharma, Ipsen, Eisai; Honoraria (self): Novartis, Medivation, Astellas Pharma; Research grant/Funding (institution): Medivation. F. Donskov: Research grant/Funding (institution): Pfizer, Ipsen. T.K. Choueiri: Advisory/Consultancy: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Prometheus Laboratories, Alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aven; Leadership role: Dana Farber Cancer Hospital, NCCN, Kidney Cancer Association, KidneyCan, ASCO; Shareholder/Stockholder/Stock options: Pionyr, Tempest Therapeutics; Honoraria (institution): NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Peloton Therapeutics, Pfizer, Cor; Research grant/Funding (institution): Pfizer, Novartis, Merck, Exelixis, Tracon Pharma, GlaxoSmithKline, Bristol Myers Squibb, AstraZeneca, Peleton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Phaarmaceuticals, Cerulean Pharma, Seatlle Genetics/Ast; Speaker Bureau/Expert testimony: Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel. D.Y.C. Heng: Advisory/Consultancy: Pfizer, Novartis, Bristol-Myers Squibb, Janssen, Astellas Pharma, Ipsen, Eisai, Merck; Research grant/Funding (institution): Pfizer, Novartis, Exelixis, Bristol-Myers Squibb, Ipsen. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

426P - A multicenter, randomized, double-blind, phase II study of lenvatinib (LEN) in patients (pts) with radioiodine-refractory differentiated thyroid cancer (RR-DTC) to evaluate the safety and efficacy of a daily oral starting dose of 18 mg vs 24 mg (ID 501)

Presentation Number
426P
Lecture Time
09:00 - 09:00
Speakers
  • Marcia S. Brose (Philadelphia, United States of America)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

In SELECT, PFS was significantly longer with LEN 24 mg/d (median: 18.3 mos) vs placebo (median: 3.6 mos; HR 0.21, 99% CI: 0.14–0.31) in pts with RR-DTC; however, the dose-reduction rate due to TEAEs was 68%. This study was designed to evaluate if a starting dose of LEN 18 mg/d could maintain efficacy and reduce toxicity in pts with RR-DTC.

Methods

In this double-blind study, pts ≥18 years (N=152) were randomized 1:1 to receive daily oral LEN at a starting dose of 24 mg (n=75) or 18 mg (n=77): ‘LEN24’ and ‘LEN18’ arms, respectively. The primary efficacy endpoint was ORR as of week 24 (ORRwk24). ORRwk24 analysis was based on a noninferiority test on the odds ratio (OR; noninferiority margin of 0.4 on OR scale). Tumors were assessed by investigators per RECIST v1.1. The primary safety endpoint was the rate of TEAEs grade ≥3 as of wk 24.

Results

The ORRwk24 was 57.3% (95% CI: 46.1–68.5) in LEN24 and 40.3% (95% CI: 29.3–51.2) in LEN18. OR (18/24 mg) 0.50 (95% CI: 0.26–0.96) did not meet criteria for noninferiority. Overall ORR was 64.0% (95% CI: 53.1–74.9) in LEN24 and 46.8% (95% CI: 35.6–57.9) in LEN18 (OR [18/24 mg] 0.50, 95% CI: 0.26–0.95). Median PFS was not reached (NR) in LEN24 (95% CI: 22.1–NR) vs 24.4 mos in LEN18 (95% CI: 14.7–NR) (HR: 1.44, 95% CI: 0.76–2.74). As of wk 24, there was a nonclinically relevant difference in the rate of TEAEs grade ≥3 of 4.2% (95% CI: −19.8–11.4 [LEN24, 61.3% of pts; LEN18, 57.1% of pts]). The most common TEAE grade ≥3 (24/18 mg) as of wk 24 was hypertension (25.3%/19.5%). Overall, TEAEs resulted in dose reduction in 69.3% of pts in LEN24 and 59.7% of pts in LEN18; 14.7% of pts in LEN24 and 16.9% of pts in LEN18 had a TEAE that led to discontinuation.

Conclusions

This study did not show noninferiority of LEN 18 mg vs LEN 24 mg based on the ORRwk24 analysis. ORRwk24 for LEN24 (57%) was consistent with that seen by investigator assessment in SELECT (59%). Incidences of grade ≥3 TEAEs through wk 24 were similar between treatment arms, and no new or unexpected safety signals were observed. These data support selection of LEN 24 mg/d as an appropriate starting dose for pts with RR-DTC.

Clinical trial identification

NCT02702388.

Editorial acknowledgement

Medical writing support was provided by Heather A. Mitchell, PhD, of Oxford PharmaGenesis, Newtown, PA and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

M.S. Brose: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Eisai; Advisory/Consultancy, Research grant/Funding (self): Blueprint Medicines; Advisory/Consultancy, Research grant/Funding (self): Loxo; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Genzyme; Advisory/Consultancy: Bristol-Myers Squibb; Research grant/Funding (self): Roche/Genentech; Research grant/Funding (self): Exelixis. B. Konda: Research grant/Funding (institution): Advanced Accelerator Applications; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Xencor; Research grant/Funding (institution): Bristol-Myers Squibb. C. de la Fouchardiere: Honoraria (self): Eisai; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Non-remunerated activity/ies: Servier; Honoraria (self), Non-remunerated activity/ies: Amgen; Honoraria (self), Non-remunerated activity/ies: Pierre Fabre Oncologie; Honoraria (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb. B.G.M. Hughes: Advisory/Consultancy: Roche; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck Sharp and Dohme; Advisory/Consultancy: Eisai; Advisory/Consultancy: Takeda; Research grant/Funding (self): Amgen. A.G. Gianoukakis: Advisory/Consultancy: Eisai; Advisory/Consultancy: Bayer; Advisory/Consultancy: Loxo-Lilly. I. Romanov: Honoraria (self): Eisai; Honoraria (self): Merck Serono; Honoraria (self): Bristol-Myers Squibb. M.K. Krzyzanowska: Advisory/Consultancy, Research grant/Funding (self): Eisai; Advisory/Consultancy: Bayer; Research grant/Funding (self): Exelixis; Research grant/Funding (self): Ipsen. T. Binder, R. Xie: Full/Part-time employment: Eisai Inc. C. Dutcus: Leadership role, Research grant/Funding (self), Full/Part-time employment: Eisai Inc. M.H. Taylor: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Loxo; Advisory/Consultancy: Bayer; Advisory/Consultancy: ArQule; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi/Genzyme. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

427P - On the clinical implications of systemic and local immune responses in human angiosarcoma (ID 610)

Presentation Number
427P
Lecture Time
09:00 - 09:00
Speakers
  • Jason Yongsheng Chan (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Angiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes.

Methods

In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry.

Results

In the overall cohort (n=150), angiosarcomas of the head and neck comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18-2.87, p=0.0073), along with age >65 years and distant metastasis at diagnosis. Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman’s rho 0.450, p=0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15+ cells, rho 0.398, p=0.0198) and macrophage (CD68+ cells, rho 0.515, p=0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodelling & metastasis and cytokine & chemokine signaling, as well as myeloid compartment scores (all p<0.001). In patients with documented best clinical responses to first-line chemotherapy (n=60), these pathway scores were all significantly higher in non-responders (47%) compared to responders.

Conclusions

These findings suggest that systemic and local immune responses may inform clinical outcomes in angiosarcomas.

Legal entity responsible for the study

The authors.

Funding

SingHealth Duke-NUS Oncology ACP.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

428P - Prognostic value of clinico-pathological characteristics and peripheral monocyte counts in localised extra-meningeal solitary fibrous tumours treated with surgical resection (ID 618)

Presentation Number
428P
Lecture Time
09:00 - 09:00
Speakers
  • Ryan M. Lim (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Solitary Fibrous Tumour (SFT) is a rare soft tissue neoplasm with an intermediate biologic potential. The aim of this study was to investigate clinical and pathological factors as well as peripheral blood counts to determine factors predicting for likelihood of early recurrence and poor survival in extra-meningeal SFTs after surgical resection.

Methods

We retrieved the records of 101 patients that were consecutively diagnosed with SFT from 1996-2019 at the National Cancer Centre Singapore and Singapore General Hospital. 19 patients were excluded from the study, of which 6 had distant metastasis at diagnosis, 5 did not undergo curative surgery and 8 were meningeal SFTs that are known to have a poor prognosis. The remaining 82 cases of extra-meningeal SFTs that underwent curative surgery were retrospectively examined with survival analyses performed using the Kaplan-Meier method and multivariate Cox proportional models.

Results

The cohort consisted of 37 men and 45 women with a median age of 51 years (range, 13-87). The primary site of the tumour was abdominopelvic in 18 (22.0%), limbs/trunk in 27 (32.9%), pulmonary/pleura in 18 (22.0%) and head/neck in 19 (23.2%). Median tumour size was 5.0 cm (range, 1.4-30.0). The 5-year overall survival (OS) and event-free survival (EFS) was 92.4% and 79.2% respectively. On univariate analysis, advanced age was prognostic for worse OS, while an abdominopelvic site, lymphocytosis (>2.2 x 109/L) and monocytosis (>0.56 x 109/L) were prognostic for both worse OS and EFS. On multivariate analysis, only age, abdominopelvic site and monocytosis remained independently prognostic for OS, while abdominopelvic site and monocytosis were retained as independently prognostic factors for EFS (all p < 0.05). Tumour depth, tumour size, resection margin, tumour necrosis and mitotic count were not significantly prognostic.

Conclusions

In extra-meningeal SFT, clinical factors including advanced age and abdominopelvic location indicate poor prognosis. In addition, peripheral monocytosis at diagnosis may serve as a novel and easily obtained biomarker for further prognostication.

Legal entity responsible for the study

National Cancer Centre Singapore.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

429P - Demographics, pattern of care, and outcome analysis of malignant melanoma cases from a tertiary care centre in India (ID 743)

Presentation Number
429P
Lecture Time
09:00 - 09:00
Speakers
  • Anshul Agarwal (Mumbai, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Melanoma care is revolutionized with checkpoint inhibitors (CPI) and targeted therapies; however, access to drugs is challenging in Low-Middle income countries (LMICs).

Methods

Histologically proven melanoma cases registered from 2013–2019 were analysed.

Results

There were 443 patients with median age of 54 years; 60% were males with 41% cutaneous, and 57% mucosal melanomas; most common primary sites were anorectal (41%) and extremities (27%); 11% were BRAF mutated. Among the 258 non-metastatic patients, the median follow up was 30 months (0–83 months). Of these, 114 (44%) had prior surgery and 73 (64%) were already metastatic at presentation to us. Of the remaining 144 (56%), 101 underwent resection, 11 were unresectable, and rest 32 did not take treatment. Median EFS of non-metastatic patients was 17 (95% CI: 11-23) months while median OS was 38 months (95% CI: 30-46); 2-years OS predictions was 66% (95% CI: 59-73). Overall metastatic cohort (n=311) comprised of baseline metastatic (n=185) and non-metastatic patients with (73) or without prior therapy (53) who failed with distant metastasis.Commonest metastatic sites were liver (52%) and non-regional nodes (51%). Median follow up in this cohort was 21 (0–74 months); 138 (44.4%) received chemotherapy(taxane, dacarbazine), Interferons, while 29 (9.3%) patients received CPI. The clinical benefit rate was 31%. In baseline metastatic cohort, the median EFS and OS with BSC alone were 3.8 (95% CI: 2.6-5.0) months and 3.5 (95% CI: 2.45-4.63) vs. 5.55 (95% CI: 3-8) months and 11 (95% CI: 9-13.1) months in any systemic therapy group (HR for OS: 0.34, 95% CI: 0.22-0.52; P<0.001). Grade 3/4 toxicity were observed in 16 % with predominance of thrombocytopenia and anemia (both 4%) in chemotherapy and anemia (10%) for CPI. Any therapy received was significant in both cohort;additionally, site, surgery, were significant in non-metastatic cohort.

Conclusions

This real-world data from India reflects the hard reality of access of expensive, standard of care therapies. Interesting finding that any systemic therapy can lead to meaningful clinical benefits at-least in a select group of patients merits exploration if standard options are not feasible, especially in LMICs.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

430P - Teenagers and young adult cancers in rural central India: Access to age-appropriate care (ID 775)

Presentation Number
430P
Lecture Time
09:00 - 09:00
Speakers
  • Runu Sharma (Indore, India)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Teenagers and young adults (age 15-29) are increasingly the focus of cancer care in India. Young persons from rural western Madhya Pradesh, a resource crunch area, need provided support, and a care pathway to ensure optimal results in the treatment of cancer.

Methods

Disease characteristics of TYA patients over (30 months) from 2018-thru 2020 were analyzed. Abandonment defined as. Failure to start / complete treatment was quantified, and the cancers were documented by the Birch classification. Early deaths (within 30 days) and trends to completion of therapy were documented. Telephonic tracing of patients, escorting them to hospital, providing accommodation, food caregiver support. Since Feb 2019, the state sponsored Insurance scheme Ayushman Bharat provided TYAs access to cancer care.

Results

Two hundred and forty six cancer patients’ records in the age group 15-29 years were. analysed in a retrospective study. Median age 23 years; M: F 166: 80. Diseases were classified by the Birch Classification: Leukemias 84; Lymphomas. 45; Brain 6; Bone tumors 55; Soft tissue tumors 6; Germ Cell tumors 19; Carcinoma 30; Miscellaneous 1; Twenty two (9%) abandoned treatment. 65 (26%) alive after completed therapy; Early deaths occurred in 56 (23%); as of 30 June 2020, 103 (41%) are alive on treatment.

Conclusions

Early deaths occurred on account of poor nutrition; delayed diagnosis; toxicity of therapy.TYAcan Foundation provided diagnostic, treatment and accommodation support; mitigating early morbidity and mortality; tracking young persons to reduce abandonment. Early trends indicate that the government Ayushman Scheme and the social entrepreneurship of TYAcan together helped establish a viable care pathway for young cancer patients to achieve to survival rates.

Legal entity responsible for the study

Department of Medical Oncology, Sri Aurobindo Institute of Medical sciences.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

431P - Quantitative study of two critical lncRNAs in patients with glioma tumours (ID 783)

Presentation Number
431P
Lecture Time
09:00 - 09:00
Speakers
  • Kamal Mohammadian (Hamadan, Iran)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Glioma is one of the most common types of tumor of the central nervous system with high morbidity and mortality. Based on this fact that the prognosis of patients with high- grade glioma is poor, it is very important to develop new diagnostic and therapeutic strategies covering more efficient methods and drugs. Recent studies have demonstrated that Long non-coding RNAs (lncRNAs) may act as potential inducers or suppressors of numerous types of tumors including glioma. Besides, there are more expression of lncRNAs than coding mRNAs and miRNAs in specific tissues.In this study we evaluated two lncRNAs including MEG3 and MDC1-AS1 which seemed to be involved in the initiation and progression of high grade Gliomas.

Methods

The expression of lncRNAs were studied on 150 paraffin tissue block samples of Iranian participants, including 37 samples of low-grade gliomas(I&II), 58 samples of high grade glioma (III& IV) and 95 samples of non-tumoral tissues. After RNA extraction and complementary DNA synthesis(cDNA), probe-based (Taqman) Real-time PCR were used to evaluate lncRNAs expression level followed by statistical analizing.

Results

Our analysis, indicates that lncRNAs including MEG3 and MDC-AS1 are down-regulated (p =0.001) in high grade glioma tumors (grade III & IV) in comparison to low grade gliomas (grade I and II) and non-tumoral tissues.

Conclusions

The results show that there are critical expression differences i n MEG3 and MDC1-AS1 lncRNAs as tumor suppressor genes between high and low-grade gliomas. Comprising with other reports, it could be assumed that expression of MEG3 and MDC1-AS1 lncRNAs may serve as potential biomarkers and also therapeutic targets for detection and treatment of glioma tumors. Key words: Quantitative, lncRNAs, glioma.

Legal entity responsible for the study

Arash Moradi.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

432P - Efficacy and tolerability of vismodegib treatment in locally advanced and metastatic basal cell carcinoma (ID 865)

Presentation Number
432P
Lecture Time
09:00 - 09:00
Speakers
  • Mustafa Gürbüz (Ankara, Turkey)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Basal cell carcinoma (BCC) is the most common cancer. Surgical excision is the primary treatment of BCC. Radiotherapy and topical therapies are other treatment options. Vismodegib inhibits the hedgehog signaling pathway that is an important mechanism of developing BCC. The study aims to evaluate the vismodegib treatment in local advanced (laBCC) and metastatic (mBCC) basal cell carcinoma.

Methods

The data of 29 patients were retrospectively reviewed. The clinical and histopathological features of the patients and adverse events of vismodegib treatment were recorded. Overall survival (OS) and progression-free survival (PFS) evaluated with Kaplan-Meier analysis.

Results

The median follow-up period was 17 months (range: 1.6-57.3). The median age at diagnosis was 73 years (range: 39-88). The percentages of female and male patients were 51.7% and 48.3%, respectively. The most common location of disease was head and neck (86.2%). The number of metastatic patients was 5 (17.2%). The most common non-skin locations of disease were lymph nodes-13.8%, bone-13.8%, lung-6.9%, and brain-6.9%. Three (10.3%) patients had Gorlin’s syndrome. Before vismodegib treatment, 15 (51.7%) patients had received radiotherapy and 18 (62.1%) patients had undergone surgery. With vismodegib treatment, the complete response rate was 27.6% and partial response 55.2%, and stable response 10.3%. Treatment responses were most frequently seen within two months from the beginning of vismodegib. The most common adverse events were fatigue-58.6%, muscle spasms-48.3%, alopecia-13.8%, and weight loss- 13.8%. A total of 8 (27.6%) patients deceased during the study period. The median OS was 43.3±9.0 months (25.6-61.1) for all patients. The median PFS in the laBCC was 15.7±1.8 months (12.2-19.3). The median PFS in the mBCC was 12.1±4.6 months (2.9-21.2). After the disease progression under vismodegib treatment, 53.8% of the patients received chemotherapy or had surgical treatment.

Conclusions

In this study, we determined that vismodegib treatment in locally advanced and metastatic BCC was well tolerated and effective.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

433P - Association between aspirin and cancer risk: A Mendelian randomization analysis (ID 885)

Presentation Number
433P
Lecture Time
09:00 - 09:00
Speakers
  • Yu Jiang (Guangzhou, China)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Previous researches have reported on the protective effect of aspirin on different types of cancers. However, evidence from observational studies can be biased by multiple confounding factors. Also, it remains unclear whether aspirin use is casually related to a decreased cancer risk. Consequently, we conducted Mendelian randomization analyses, using single nucleotide polymorphisms (SNPs) as instrumental variables to investigate the casual effect of aspirin on different types of cancers.

Methods

Mendelian randomization analyses were conducted using pooled statistics from corresponding researches and several large-scale consortia. Inverse-variance weighted, MR-Egger and weighted median methods were utilized to evaluate the possible causal relationship between aspirin and the observed reduction in cancer risk. Results were shown by odds ratios (OR) and their corresponding 95% CIs. Analyses were conducted using the package “TwoSampleMR” in R.

Results

A total of 19 cancers corresponding to 344,392 cases and 5,424,758 controls were included in the final analysis. In contrast to the lower risk for various cancer types reported in conventional observational studies, our MR results only showed a decreased risk in lung cancer [odds ratio (OR) 0.0418; 95% confidence interval (CI) 0.0031-0.5638; P=0.0168] and squamous cell lung cancer [OR=0.002; 95% CI 1.2145×10-5-0.3009; P=0.0153]. Insignificant results were observed in other types of cancers including lung adenocarcinoma, breast cancer, ovarian cancer, colon cancer, kidney cancer, liver cancer, esophageal cancer, oral cancer, pancreas cancer, rectal cancer, malignant melanoma, non-melanoma skin cancer, Hodgkin’s lymphoma as well as non-Hodgkin’s lymphoma.

Conclusions

The potential effect of aspirin in cancer prevention still needs to be interpreted with cautions and aspirin is still too early to be recommended as a universal chemoprotective agent for primary cancer prevention. Further randomized controlled trials with a more rigorous design are warranted in the future.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

434P - Pan-Canadian evidence-based, consensus-driven cancer treatment protocols/information for use at the point of care by medical oncologists? Is there a need? (ID 889)

Presentation Number
434P
Lecture Time
09:00 - 09:00
Speakers
  • Kiran Virik (Kingston, NS, Canada)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

A number of provincial online treatment guidelines/protocols exist in Canada, which differ in the information contained and the ease of use. Currently there is no national evidence-based, consensus-driven cancer treatment protocol for use at the point of care. The aim of such a resource would be to support Medical Oncologists (MOs) in the delivery of cancer treatment at the clinic interface and potentially improve patient outcomes by reducing treatment variation across Canada.

Methods

The study was conducted in two stages. Available provincial cancer treatment protocols were evaluated with regards to: content for chemotherapy, immunotherapy, ease of use, toxicity, dosing recommendations, reference studies. Canadian MOs were invited to participate in an anonymous survey distributed through the Canadian Association of Medical Oncologists. The assessment included: current online resources (OR) used, information provided, ease of use, relevance to point of care use, need for a national Canadian resource. MOs were asked to review a comparator Pan-Australian OR.

Results

40/327 responded: 28% BC, 26% ON and the rest from other provinces. 82%, 54% and 23% respectively used the BC and ON and other provincial ORs. 50% used ≥2 websites. 62% found the website of choice easy to use, 33% felt it had updated immune therapy information and 26% felt it was updated regularly. The OR used met the MO need for dose/scheduling in 87.5% cases but only 50% and 37.5% cases for AEs and reference information respectively. Criteria evaluated in the ORs included: dosing, toxicity modification, AEs, monitoring, references and other criteria. 95% of MOs felt that a single portal aimed at point of care for Canadian MOs would be of value. 64% felt that the international comparator was better than the current OR being used.

Conclusions

There is variation in the current Canadian OR used by MOs in Canada with a need for national evidence-based, cancer treatment protocols/information for use at the point of care. To develop such a Pan-Canadian website resource, further analysis and infrastructure is required. Such a resource would potentially reduce treatment variability and augment quality of care delivered.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

435P - Hypnotics and risk of cancer: A meta-analysis of observational studies (ID 891)

Presentation Number
435P
Lecture Time
09:00 - 09:00
Speakers
  • Tzu Rong Peng (New Taipei City, Taiwan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

The association between hypnotic drugs and risk of cancer remains controversial. Therefore, we performed a meta-analysis to investigate this association.

Methods

Pubmed and Embase were searched systematically were searched to identify publications up to May 2020. The Newcastle-Ottawa scale for observational studies was used to assess the quality of studies. All included studies were evaluated by two reviewers independently; any discrepancies were resolved through discussion.

Results

A total of 28 observational epidemiological studies including 22 case-control studies and 6 cohort studies with 340,614 hypnotics users and 1,828,057 non-users were included in the final analyses. Hypnotics (benzodiazepines and Z-drugs) use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.17; 95% confidence interval 1.09–1.26) in a random-effects meta-analysis of all studies. Subgroup meta-analyses by various factors such as study design, type of case-control study, study region, and methodological quality of study showed consistent findings. Also, a significant dose-response relationship was observed between the use of hypnotics and the risk of cancer.

Conclusions

This meta-analysis revealed association between use of hypnotics drugs and risk of cancer. However, a high heterogeneity was observed among identified studies and results were inconsistent in some subgroups. Randomized control trials are needed to confirm the results in future.

Editorial acknowledgement

This study was supported by grants from the Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-109-18).

Legal entity responsible for the study

The author.

Funding

Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation.

Disclosure

The author has declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

436P - Clinicopathological characteristics and outcomes of adolescent and young adult (AYA) melanoma: Results from an Asian perspective (ID 925)

Presentation Number
436P
Lecture Time
09:00 - 09:00
Speakers
  • Wei Lin Goh (Singapore, Singapore)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

AYA melanomas (diagnosed 16-39 years) are rare but rising in incidence. It is not well-understood how they differ from adult melanomas. We aim to describe the demographics, clinic-molecular characteristics and outcomes from our institution.

Methods

We retrospectively reviewed all melanoma patients diagnosed between 16 and 39 years old (y) who presented to the National Cancer Centre Singapore from 1 January 2000 to 31 March 2019.

Results

There were 74 patients (41 females, 33 males). 51.4% (n=38) were Chinese, 9.5% Caucasians, 6.8% Malays and the rest of other ethnicity. Across age groups, 9 patients were 16-23 y (12.2%); 26 between 24-31y (35.1%) and 39 between 32-39y (52.7%). The most common subtype was cutaneous melanoma (46%, n=34). 31 (41.9%) patients had BRAF testing. 46.4% (n=13) had BRAF V600E mutation and 1 had BRAF V600K. 20 (27.0%) were tested for cKIT, with none having mutations. 51.4% (n=38) had stage I/II disease (American Joint Committee on Cancer 7th Edition), 16 with stage III and 10 had stage IV. Common metastatic sites were lungs, lymph nodes and liver. 25 (33.8%) patients had sentinel lymph node biopsy (SLNBx), with 5 having lymph node dissection. Among those with SLNBx, 4, 13 and 5 patients had Breslow depths of <1mm, 1-4mm and >4mm respectively. The median depth was 2.7mm (range 0.25–9mm). 7 (9.5%) had first-line systemic therapy, with 5 (2 stage IV; 2 stage III and 1 unknown) receiving immunotherapy. 2 (stage IV) had combination chemotherapy (Dacarbazine/Cisplatin and Paclitaxel/Bevacizumab/Caroboplatin). None received BRAF inhibitors. The median overall survival (OS) is 2.7y (range 0.1–17.7y) for all and 1y for metastatic disease. The 5y OS is 34.5%. The breakdown is shown in the table.

Survival by age and stage

Number Median OS p-value
16-23y 9 4.53 =0.15
24-31y 26 4.15
32-39y 39 2.51
Stage I-III 54 3.25 <0.001
Stage IV 10 1.01

Conclusions

Routine BRAF/cKIT testing commenced in 2010 and immunotherapy started only in 2017, contributing to outcomes we see. Poorer survival is associated with higher stage (p<0.001). Further studies are needed to elucidate potential biological and cancer-specific differences between AYAs and adult melanoma population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

437P - Long-term efficacy and toxicity outcome of adjuvant external beam radiotherapy for medullary thyroid cancer: A single institution cohort study (ID 986)

Presentation Number
437P
Lecture Time
09:00 - 09:00
Speakers
  • Ka Man Cheung (Kowloon, Hong Kong PRC)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Medullary thyroid cancer (MTC) is a relatively aggressive entity with high risk of locoregional recurrence and distant metastases. There is no role for adjuvant radioactive iodine and medical treatment, while adjuvant external beam radiotherapy (EBRT) remains controversial. Guidelines and a recent systematic review suggested EBRT for extensive disease, which includes nodal involvement, extrathyroidal extension and residual disease, but data remained scarce. Toxicity of EBRT was inconsistently reported.

Methods

All consecutive patients diagnosed with MTC who received curative intent treatment from 2000 to 2018 in a tertiary institution were included. All patients received total thyroidectomy, prophylactic central compartment dissection and as-required therapeutic lateral compartments dissection. Patients at high risk of relapse (R1-2 resection, cervical lymph node metastases, extrathyroidal extension) were offered adjuvant EBRT. Radiotherapy volume covered thyroid bed and level II - VI. The whole treated volume received 60Gy with additional boost to gross residual up to 66Gy. Relapse, survival and toxicity outcomes were reported.

Results

41 patients were included, median follow-up was 12 years. Median age was 48.8, 34 (82%) patients were of pT1/2 and19 (38%) were pN1. 4 (8%) underwent R1 resection and 2 (4%) had gross residual disease despite maximal resection. 19 (46%) completed EBRT. Despite at high risk, only 3 (15.7%) had locoregional relapse after EBRT compared to 2 (9%) in those not required. Higher incidence of distant metastases in EBRT group (5 compared to 2) may reflect more advanced underlying disease. Overall survival was similar (both not yet reached median, p=0.31). Acute side effects of EBRT were well tolerated, with all patients experiencing only G1/2 mucositis and dermatitis. None required hospitalisation due to side-effects nor artificial nutrition. No G3/4 long term side-effects were observed.

Conclusions

Adjuvant EBRT in advanced MTC results in encouraging locoregional control and low incidence of significant short and long-term side-effects.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

438P - Real-world data of relapse after adjuvant treatment (Tx) in high-risk melanoma (ID 1001)

Presentation Number
438P
Lecture Time
09:00 - 09:00
Speakers
  • Carolina Ortiz Velez (Barcelona, Spain)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Adjuvant (adj) Tx with programmed cell death protein 1 (PD-1) inhibitors or targeted therapy (TT) for 1 year in patients (pts) with high-risk resected melanoma prolongs relapse-free survival (RFS). However, up to 1/3 of pts recur in the year after adj Tx and there are few data regarding patterns of relapse, management and outcomes. Our aim was to describe how adj Tx impacts the outcomes in melanoma pts in our center.

Methods

Single-institution experience of 123 consecutive pts with melanoma resected in our center from 2014 to 2019 were retrospectively analyzed. Clinicopathological factors, adj Tx, timing and patterns of relapse, Tx at relapse and subsequent outcomes were examined.

Results

Median age at diagnosis was 57 years, 45% were male and BRAF-mt was found in 38%. Stage III A/B/C/D or IV was 6%, 10%, 19%, 1% and 1%, respectively. Sentinel node biopsy was performed in 80% and lymphadenectomy in 33% of 123 pts. A total of 49 pts received adj Tx: 3 pts (6%) TT, 8 pts (16%) IFN-α, and 38 pts (31%) immunotherapy (iTx) with anti-PD-1 and/or ipilimumab. A total of 40 pts (32%) had relapse (65% locoregional and 35% distant), 8 pts (21%) had prior adj iTx with a median RFS of 21.5 months (m) (CI95%17.4-NA). 24 pts (60%) were resected (6 pts with distant recurrent), 14 pts received adj Tx (12 pts iTx, 1 pt IFN-α and 1 pt TT), for 4-pts was the second adj Tx. A total of 31 of 123 pts (25%) developed metastatic melanoma (MM), of these 17 pts (55%) received adj Tx. PFS at 1st line of Tx of pts with prior adj-Tx vs no was similar (HR=1.01, p=0.98), mainly Tx were iTx (65%), TT (31%) and chemotherapy (4%). Remarkably, there was no worse response rate (complete response [CR] or partial response [PR]) in pts with prior adj Tx (68.8% vs 35.7%, p=0.14). Of 17 pts with prior adj-Tx (16 pts adj-iTx) who had MM, twelve (70.6%) received iTx at 1st line, 50% had response to iTx. Also, all 4 pts BRAF-mt with prior adj iTx who received TT at 1st line had CR or PR. There was no correlation between treatment-free interval after adj TX and PFS at 1st line (p=0.66).

Conclusions

Our real-world data demonstrates that after a locoregional or distant relapse of melanoma, despite prior adj-Tx, Tx with iTx or TT can be active. But additional research is needed.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R. Dienstmann: Advisory/Consultancy: Roche, Boehringer Ingelheim; Honoraria (self): Roche, Ipsen, Amgen, Servier, Sanofi, Merck Sharp & Dohme; Research grant/Funding (self): Merck, Pierre Fabre. E. Muñoz-Couselo: Advisory/Consultancy: BMS; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

439P - Immunohistochemical analysis of p53 and Ki-67 in glioblastoma (GBM) and their correlations with patient survival (ID 1004)

Presentation Number
439P
Lecture Time
09:00 - 09:00
Speakers
  • Paulo J. Luz (Faro, Portugal)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

GBM is the most common and agressive primary brain tumor with a median survival around 12-14 months. Detection of prognostic factors will be very important in planning and selecting treatment for patients with this disease. Association of TP53 mutations and Ki67 proliferation index with survival outcome in GBM patients has not been consistente. Aim: the aim of our study were to determine the expression of p53 and Ki67 in our cohort of GBMs patients, and to determine their correlation with patient survival.

Methods

This study is based on samples prospectively collected from 65 patients with glioblastoma. Samples were collected from Centro Hospitalar Universitário do Algarve during the period extending from January 2016 to June 2019. p53 and Ki67 expression was assessed immunohistochemically on Formalin Fixed Paraffin-Embedded tissues. Kaplan-Meier analysis were carried out in each group.

Results

The mean age of the 65 patients (38 males and 27 females) was 63 years old. A total of 53 patients underwent resection and 12 to biopsy. 20 patients completed Stupp Protocol. The median survival time for all patients was 42,1 weeks, A total of 53.8% exhibited p53 overexpression (p53+). Median survival time (with 95% confidence intervals) was 26.7 weeks for patients with p53+ tumors and 48.6 weeks for those with p53-negative tumors (p=<0.05). Ki67 >20% was correlated to poor survival however it was not statistically significant.

Conclusions

In our cohort, p53 expression had strong prognostic value. GBM is characterized by extreme heterogeneity which can affect diagnostic accuracy as well the outcome after surgical treatment. A better understanding of the molecular behaviour could help us planning treatment and developing new targets.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

440P - Blinded independent central review of oncology trials: The monitoring of readers' performance (ID 419)

Presentation Number
440P
Lecture Time
09:00 - 09:00
Speakers
  • Hubert Beaumont (Valbonne, France)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

For image-based evaluations, RECIST 1.1 remains the most used criteria for assessing the therapeutic response in clinical trials. The variabilities of evaluations are generally mitigated by double reading the images, with a third reader adjudicating the discrepancies. Blinded independent central review (BICR) with double read and adjudication is a complex management that needs to be closely monitored. The rate of inter-reader discrepancies is one of those metrics of choice for detecting quality issues in trials. The aim of our study was to provide reference values metrics for the monitoring of RECIST 1.1 BICR with double read plus adjudication in clinical trials.

Methods

From the list of clinical trials recorded in the Median Technologies database, we selected a subset of trials according to the following inclusion criteria: 1) Phase II and III 2) Response criteria: RECIST, 3) Trial status: completed, 4) Trial setting: central double read with adjudication, 5) Trial endpoint: Overall Response and PD and 6) Readers monitoring was enabled. For the selected trials, we analyzed, per trial and per readers, the rate of inter-reader discrepancy and the rate of readers’ endorsement by the adjudicator. We compared the discrepancy rate between the indications using Marascuillo test.

Results

Out of the 103 recorded trials, 5 conformed the inclusion criteria. Their indications were: Lung (1), Skin (1) biliary track (1), Gastric (1) and multiple (1) cancers. A total of 1561 patients (mean=312/per trial) and 5986 time points (mean=1197/per trial) were analyzed by 25 readers; 8 adjudicators were involved. Per reader, the discrepancy rate ranged from 27.4% to 68.5% (mean=50.1%) with an endorsement rate ranging from 11.5% to 91.1%. Per trial, the average discrepancy rate was 50.8% [33.0-63.8]. We found a significant difference in the rate of discrepancy per indications: Biliary (63.8%) vs Multiple cancers (33.0%) (p<0.001).

Conclusions

In BICR clinical trials with double reads and adjudication, readers’ monitoring is highly recommended. Monitoring metrics reported a wide range of discrepancy rate and of individual readers performances. Discrepancy rate and readers performances would be indication dependent.

Legal entity responsible for the study

Beaumont Hubert.

Funding

Has not received any funding.

Disclosure

H. Beaumont, A. Iannessi, J. Cillario, Y. Liu: Full/Part-time employment: Median Technologies.

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e-Poster Display Session (ID 87) Poster Display

441P - Influence of radiation therapy of patients with somatotropic pituitary adenomas depending on the age of patients (ID 828)

Presentation Number
441P
Lecture Time
09:00 - 09:00
Speakers
  • Saodat S. Issaeva (Tashkent, Uzbekistan)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

To evaluate the effectiveness of radiation therapy (RT) in patients with somatotropic pituitary adenomas, depending on the age of patients and the activity of pituitary adenomas.

Methods

The subject of the study were 50 patients (women-36, men-14) with acromegaly who received gammatherapy in a total dose of 45-60Gr of 20-25fractions every other day. The duration of the disease was 15years on average. In general, the age of patients ranged from 26 to 77years, on average-44.7±6.8years. By age, the patients were divided into 3 groups: the I age group-29-44years-23patients (46%), the IIgroup-45-59year-16patients (32%), the IIIgroup-60-79years, 11patients (22%). All patients underwent hormonal (GH, IGF-1) studies.

Results

The levels of hormones of GH and IGF-1 remained high in the I group in 22% of patients, and in group III in 9%. Remissions reached 64% in the III age group. The highest level of GH content occurred in the age range from45 to59years and was 77.5±9.68mMе/l, and from 26 to 44years it was 68.1±6.84mMе/l. After RT, this indicator in both age groups was almost equally suppressed, but not up to the norm. The decrease in the GH level to normal was observed in I age group in 8patients, and in the II age group in 5patients it was 2.65±2.2mMе/l and 2.23±1.4mMе/l, respectively. In group III, in 11 patients before RT, the mean level of GH was 46.5±8.2mMе/l. After RT, the level of GH decreased in this way: not suppressed only in one patient and was 22.1±0.89mMе/l, in 3patients the level of GH was suppressed, but not up to the norm and amounted to6.7±0.7mMe/l, only 7patients were suppressed and amounted to 2.46±2.2mMe/l.

Conclusions

In all age periods, even in the period of the most activity pituitary adenoma-at the age of 26-44 years, RT is a rather effective method of treatment and gives positive results in most cases.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

442P - Results from the registrational phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET mutation-positive medullary thyroid cancer (RET+ MTC) (ID 731)

Presentation Number
442P
Lecture Time
09:00 - 09:00
Speakers
  • Bhumsuk Keam (Seoul, Korea, Republic of)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Pralsetinib is a highly potent, selective RET inhibitor targeting oncogenic RET alterations. We provide the registrational data for pts with RET+ MTC from the ARROW study.

Methods

ARROW (75 sites in 11 countries; NCT03037385) consists of a phase I dose escalation to establish the recommended phase II dose (400 mg once daily [QD] orally), and phase II expansion cohorts defined by tumor type and/or RET alteration. Primary phase II objectives are overall response rate (ORR; blinded independent central review per RECIST v1.1) and safety. We report efficacy for response-evaluable pts (REP) with RET+ MTC and safety for all pts who initiated pralsetinib 400 mg QD, both as of data cut-off date February 13, 2020.

Results

In 79 REP with RET+ MTC (mutation: 61% M918T, 28% C634X, 4% V804X, 8% other), ORR was 65% (95% CI 53–75; n=51/79, 5% complete response [CR]; 59% partial response [PR; 1 pending confirmation]). ORR for pts with prior cabozantinib and/or vandetanib (C/V) was 60% (95% CI 46–74; n=32/53; 2% CR; 58% PR [1 pending]) and in treatment-naïve pts ORR was 74% (95% CI 49–91; n=14/19; 5% CR; 68% PR; all confirmed). Disease control rate was 97% (95% CI 91–100); 99% (78/79) of pts experienced tumor shrinkage. Median progression-free survival (PFS) and duration of response (DOR) were not reached. In pts previously treated with C/V, 18-month (mo) PFS was 71% (95% CI 58–85), and 18-mo DOR was 90% (95% CI 77–100). In treatment-naïve pts, 18-mo PFS was 85% (95% CI 65–100) and 86% (12/14) of responses were ongoing at data cut-off (up to 15 mo). Responses occurred regardless of RET genotypes (somatic or germline), including 5 of 6 pts with V804X gatekeeper mutation. In the safety population (n=438), treatment-related adverse events (TRAEs) were primarily grade 1–2; most common any-grade TRAEs were increased aspartate aminotransferase (34%), anemia (24%), increased alanine aminotransferase (23%), constipation (23%) and hypertension (22%). 4% of pts discontinued due to TRAEs.

Conclusions

Pralsetinib demonstrated potent and durable clinical activity in RET+ MTC regardless of prior treatment with approved multikinase inhibitors or RET-mutation and was well tolerated.

Clinical trial identification

NCT03037385.

Editorial acknowledgement

Medical writing support was provided by Cristina Tomas, PhD, and editorial support by Sinead Stewart, both of Paragon, Knutsford, UK, supported by Blueprint Medicines Corporation.

Legal entity responsible for the study

Blueprint Medicines Corporation.

Funding

Blueprint Medicines Corporation.

Disclosure

B. Keam: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): MSD Oncology; Advisory/Consultancy: ABL Bio; Advisory/Consultancy: Genexine; Advisory/Consultancy: Cellid; Research grant/Funding (self): Ono Pharmaceutical. M.I. Hu: Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Eli Lilly & Co; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Veracyte. V. Subbiah: Research grant/Funding (institution): Roche/Genentech, Bayer, GlaxoSmithKline; Research grant/Funding (institution): Nanocarrier, Vegenics, Celgene; Research grant/Funding (institution): Northwest Biotherapeutics, Berghealth; Research grant/Funding (institution): Fujifilm, Pharmamar, D3, Pfizer, Multivir, Amgen, AbbVie; Research grant/Funding (institution): Alfa-sigma, Agensys; Research grant/Funding (institution): Boston Biomedical, Idera Pharma; Research grant/Funding (institution): Inhibrx, Exelixis; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Altum, Dragonfly Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Takeda, National Comprehensive Cancer Network, NCI-CTEP; Research grant/Funding (institution): UT MD Anderson Cancer Center, Turning Point Therapeutics; Research grant/Funding (institution): Boston Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: ASCO, ESMO, Pharmamar; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Incyte; Advisory/Consultancy, Travel/Accommodation/Expenses: Helsinn; Advisory/Consultancy: Eli Lilly, R-Pharma US; Advisory/Consultancy: QED Pharma; Advisory/Consultancy, Research grant/Funding (institution): MedImmune; Advisory/Consultancy, Other relationship: Medscape. L. Wirth: Advisory/Consultancy: Bayer; Advisory/Consultancy: Blueprint Medicine; Advisory/Consultancy: Cue Biopharma; Advisory/Consultancy: Eisai; Advisory/Consultancy: Exelexis; Advisory/Consultancy: Genentech; Advisory/Consultancy: Lilly; Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Merck; Advisory/Consultancy: Rakuten Medical. M. Schuler: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: MorphoSys; Honoraria (self): MSD; Honoraria (self): Roche Pharma AG; Licensing/Royalties, Institution has Patents, Royalties, Other Intellectual Property of Highly sensitive method for mutation detection by PCR: West German Cancer Center Essen, University Hospital Essen. A.S. Mansfield: Honoraria (institution): AbbVie; Honoraria (institution): AstraZeneca; Honoraria (institution): BMS; Honoraria (institution): Genentech/Roche; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Verily; Non-remunerated activity/ies: Mesothelioma Applied Research Foundation. M.S. Brose: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self): Raffo; Honoraria (self), Research grant/Funding (self): Exelixis; Advisory/Consultancy: Loxo; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (self): Lilly; Research grant/Funding (self): Blueprint Medicines Corporation. G. Curigliano: Advisory/Consultancy, Speaker Bureau/Expert testimony, Company Comment on Phase I-II studies: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nanostring; Speaker Bureau/Expert testimony, Non-remunerated activity/ies, Writing engagement, Company Comment on Phase I-II studies: Novartis; Speaker Bureau/Expert testimony, Non-remunerated activity/ies, Writing engagement, Company Comment on Phase I-II studies: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Company Comment on Phase I-II studies: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Foundation Medicine; Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celltrion; Advisory/Consultancy, Scientific Affairs Group: Ellipsis; Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Mylan; Non-remunerated activity/ies, Company Comment on Phase I-II studies: Sanofi Phase I-II studies; Non-remunerated activity/ies, Company Comment on Phase I-II studies: Celgene; Non-remunerated activity/ies, Company Comment on Phase I-II studies: Servier; Non-remunerated activity/ies, Company Comment on Phase I-II studies: Orion, AstraZeneca, Seattle Genetics; Non-remunerated activity/ies, Company Comment on Phase I-II studies: AbbVie, Tesaro, Merck Serono; Non-remunerated activity/ies, Company Comment on Phase I-II studies: Merck Sharp Dome, Jassen Cilag, Philogen; Non-remunerated activity/ies, Company Comment on Phase I-II studies: Bayer, Medivation, MedImmune. S. Leboulleux: Advisory/Consultancy: Lilly; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Eisai. V.W. Zhu: Honoraria (self): AstraZeneca; Honoraria (self): Roche-Foundation Medicine; Honoraria (self): Roche/Genentech; Honoraria (self): Takeda; Shareholder/Stockholder/Stock options: TP Therapeutics. I. Matos: Research grant/Funding (self), ESMO Research Fellowship sponsored by Roche: Roche. D. Adkins: Honoraria (self): Lilly; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Merck; Honoraria (self): Cue; Honoraria (self): Aduro; Honoraria (self): Kura; Honoraria (self): Oncolys; Honoraria (self): Enzychyme; Honoraria (self): Matrix; Honoraria (self): Celldex. C.S. Baik: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Calgene Inc.; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Genentech Inc.; Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): BluePrint Medicines; Research grant/Funding (institution): Daiichi Sankyo Inc.; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): TP Therapeutics; Research grant/Funding (institution): Lilly Oncology. G. Lopes: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: E.R. Squibb Sons, LLC; Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution): MSD; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Blueprint Medicines Corporation; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): BMS; Research grant/Funding (institution): GSK; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Lilly. D. Sarker: Honoraria (self), Spouse/Financial dependant, Honoraria: from Pfizer to an immediate family member: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses, Spouse/Financial dependant, Consulting/advisory role to an immediate family member: Eisai; Advisory/Consultancy: Novartis; Advisory/Consultancy: Surface Oncology; Speaker Bureau/Expert testimony: MSD Oncology; Travel/Accommodation/Expenses: MiNA Therapeutics. H. Zhang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Blueprint Medicines Corporation. C.D. Turner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Celldex; Shareholder/Stockholder/Stock options, Full/Part-time employment: Blueprint Medicines Corporation. M.H. Taylor: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Array BioPharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Loxo; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: ArQule; Advisory/Consultancy, Travel/Accommodation/Expenses: Blueprint Medicines; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi/Genzyme; Speaker Bureau/Expert testimony: Merck; Research grant/Funding (institution): Abreos Biosciences; Research grant/Funding (institution): Arch Oncology; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Novartis pharma SAS; Travel/Accommodation/Expenses: Eisai Europe Ltd. C-C. Lin: Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Boehringer-Ingelheim; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy: Takeda; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Roche; Travel/Accommodation/Expenses: BeiGene; Travel/Accommodation/Expenses: Eli Lilly. All other authors have declared no conflicts of interest.

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e-Poster Display Session (ID 87) Poster Display

443TiP - A multicenter, open-label, randomized phase II study to compare the efficacy and safety of lenvatinib in combination with ifosfamide and etoposide versus ifosfamide and etoposide in children, adolescents, and young adults with relapsed or refractory osteosarcoma (OLIE; ITCC-082) (ID 450)

Presentation Number
443TiP
Lecture Time
09:00 - 09:00
Speakers
  • Nathalie Gaspar (Villejuif, France)
Location
On-Demand e-Poster Display, Virtual Meeting, Virtual Meeting, Singapore
Date
20.11.2020
Time
09:00 - 20:00

Abstract

Background

Osteosarcoma is a bone malignancy that occurs primarily in adolescents and young adults. Approximately 30% of patients (pts) with localized disease and 80% of pts with metastatic disease at diagnosis will relapse. Lenvatinib (LEN) is a multikinase inhibitor that directly inhibits tumor growth, and may increase the uptake of chemotherapy into tumor tissue by inhibiting angiogenesis. In a phase I/II study (E7080-G000-207; ITCC-050), LEN (14 mg/m2 dose) + ifosfamide (I) + etoposide (E) demonstrated a PFS rate at 4 months (PFS-4m) of 80% (95% CI: 61–91), with a manageable safety profile in pts with relapsed/refractory osteosarcoma (Gaspar ESMO 2019). This study aims to confirm the activity of LEN + I and E that was observed in the completed phase I/II study.

Trial design

This study will evaluate LEN in combination with I and E in pts (proposed N=72, with randomization of at least 32 pts < 18 yrs old) aged 2 to 25 yrs with confirmed diagnosis of osteosarcoma that is refractory or relapsed following 1-2 prior systemic treatments. Pts previously treated with I and E are eligible, except those with a history of I-related grade ≥ 3 nephrotoxicity or encephalopathy. Randomization will be stratified by time to first relapse/refractory disease (< 18 or ≥ 18 mos) and by age (< 18 or ≥ 18 yrs). Pts in arm A will receive daily oral LEN 14 mg/m2 + I 3000 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles) and E 100 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles). Pts in arm B will receive I 3000 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles) and E 100 mg/m2/day (IV, Days 1-3 of each cycle for ≤5 cycles). Treatment will occur in 21-day cycles. The primary objective is PFS-4m by independent imaging review (IIR) using RECIST 1.1 (% of pts alive without progressive disease at week 18). Secondary objectives include PFS, OS, ORR, safety and tolerability, LEN pharmacokinetics characterization in pts in arm A, and quality of life. Tumor assessments will be performed by the investigator every 6 wks. Disease progression must be confirmed by IIR. All AEs will be recorded.

Clinical trial identification

NCT04154189.

Editorial acknowledgement

Medical writing support was provided by Heather A. Mitchell, PhD, of Oxford PharmaGenesis, Newtown, PA and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

N. Gaspar: Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy: Ipsen. Q. Campbell-Hewson: Travel/Accommodation/Expenses: Eisai. S.S. Bielack: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Lilly; Advisory/Consultancy: Sensorion; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Loxo. F. Bautista: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Travel/Accommodation/Expenses: Jazz Pharmaceuticals; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: EUSA Pharma; Travel/Accommodation/Expenses: Takeda. C. Meazza: Speaker Bureau/Expert testimony: Takeda. K. Janeway: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Amgen. D.A. Morgenstern: Advisory/Consultancy: Boehringer-Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Travel/Accommodation/Expenses: EUSA Pharma. L. Dutta, J. McKenzie, K. O'Hara, J. Huang, C.E. Okpara: Full/Part-time employment: Eisai. B. Bidadi: Full/Part-time employment: Merck & Co. Inc.; Shareholder/Stockholder/Stock options: Merck. All other authors have declared no conflicts of interest.

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