Poster display session Poster Display

371P - Clinical utility of Encyclopedic tumour analysis to treat patients advanced refractory head and neck cancers

Presentation Number
371P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Rajnish Nagarkar
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Rajnish Nagarkar
  • Darshana Patil
  • Vijay Palwe
  • Vineet Datta
  • Ashwini Ghaisas
  • Navin Srivastava
  • Ajay Srinivasan
  • Dadasaheb Akolkar
  • Rajan Datar

Abstract

Background

Head and Neck Squamous Cell Carcinomas (HNSCC) account for 4.5% of global cancer incidences and mortality respectively. In India however, HNSCC accounts for 17% of cancer related incidences and 15% of cancer related mortality. Standard of Care (SoC) systemic treatment approaches for HNSCC are based on randomized clinical trials which do not sufficiently consider patient specific features of the tumor. We evaluated the efficacy of personalized treatment in a cohort (n = 31) of advanced refractory HNSCC, where patient-specific treatment regimens were based on Encyclopedic Tumor Analysis (ETA).

Methods

Freshly biopsied tumor tissue and peripheral blood of patients were used for integrational multi-analyte investigations as part of ETA, which included gene alterations and gene expression, as well as in vitro chemosensitivity and response profiling (CRR) of viable tumor cells. Patients received individualized therapy recommendations based on ETA. All patients underwent whole body PET-CT and brain MRI scans prior to start of treatment, and follow-up scans every 6-8 weeks. Treatment response was evaluated as per RECIST 1.1 criteria.

Results

Among the 31 patients who received personalized treatment guided by ETA, partial response (PR) was observed in 14 patients and Stable Disease (SD) in 16 patients yielding an Objective Response Rate (ORR) of 45.2% and Clinical Benefit Rate of (CBR) 96.8%, respectively. Patients were followed up for a median of 146 days (Range 42 – 368). At most recent follow-up 1 patient showed disease progression, whereas Progression Free Survival was observed in 30 patients. Median Progression-Free Survival was 146 days. No grade IV adverse events were observed. There were no treatment related deaths. Most common Grade III adverse events included Fatigue, Anorexia, Thrombocytopenia, Neutropenia and Oral Mucositis. Most patients reported qualitative improvements in symptomatic and functional status.

Conclusions

ETA guided treatments can offer viable treatment options in advanced refractory HNSCC yielding meaningful ORR and disease control in majority of patients.

Legal entity responsible for the study

The Authors.

Funding

Datar Cancer Genetics Limited.

Disclosure

R. Nagarkar: Advisory / Consultancy: Datar Cancer Genetics Limited. D. Patil: Full / Part-time employment: Datar Cancer Genetics Limited. V. Palwe: Non-remunerated activity/ies: Datar Cancer Genetics Limited. V. Datta: Full / Part-time employment: Datar Cancer Genetics Limited. A. Ghaisas: Full / Part-time employment: Datar Cancer Genetics Limited. N. Srivastava: Full / Part-time employment: Datar Cancer Genetics Limited. A. Srinivasan: Full / Part-time employment: Datar Cancer Genetics Limited. D. Akolkar: Full / Part-time employment: Datar Cancer Genetics Limited. R. Datar: Leadership role, Shareholder / Stockholder / Stock options, Licensing / Royalties: Datar Cancer Genetics Limited.

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Mini Oral session - Developmental and precision medicine Mini Oral session

365O - Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer

Presentation Number
365O
Lecture Time
03:10 PM - 03:15 PM
Speakers
  • Daniel Shao Weng Tan
Location
Room 311, Singapore, Singapore, Singapore
Date
Fri, 22.11.2019
Time
03:00 PM - 04:00 PM
Authors
  • David Hyman
  • Daniel Shao Weng Tan
  • Cornelis Van Tilburg
  • Catherine Albert
  • Birgit Geoerger
  • Anna Farago
  • Ted Laetsch
  • Shivaani Kummar
  • Francois Doz
  • Ulrik Lassen
  • Steven Dubois
  • Ray McDermott
  • Leo Mascarenhas
  • Jordan Berlin
  • Erin Rudzinski
  • Shivani Nanda
  • Barrett Childs
  • Alexander Drilon
  • David S. Hong

Abstract

Background

Genomic rearrangements involving neurotrophic tropomyosin receptor kinase 1, 2, or 3 (NTRK1/2/3) result in constitutively active tropomyosin receptor kinase (TRK) fusion proteins that are oncogenic drivers in multiple pediatric and adult cancers. Larotrectinib is a selective TRK inhibitor approved by the US Food and Drug Administration in 2018 for the treatment of TRK fusion cancer based on a primary analysis in 55 patients from 3 clinical trials [Drilon et al. NEJM 2018]. Here, we report median duration of response (DOR) data in the primary cohort and updated data in an expanded cohort of 159 patients with TRK fusion cancer treated with larotrectinib, with 153 (55 primary + 98 supplemental) evaluable for efficacy.

Methods

Patients with TRK fusion cancer detected by local molecular profiling were treated with larotrectinib across 3 studies (NCT02122913, NCT02637687, NCT02576431). Disease status was assessed by investigators using RECIST 1.1. Data cut-off was February 19, 2019.

Results

In the primary cohort of 55 patients with a median follow-up of 26 months, the median DOR in 44 patients with complete or partial responses was 35.2 months (95% CI 21.2–not evaluable [NE]), with 17 progression events and 27 responses ongoing (range 1.6–44 months). Median progression-free survival in the primary cohort was 25.8 months (95% CI 9.9–NE), with 27 patients having progressed. In the expanded combined dataset, the most common tumor types included soft tissue sarcoma (n = 36), infantile fibrosarcoma (n = 29), thyroid carcinoma (n = 26), salivary gland carcinoma (n = 21), and lung cancer (n = 12). Median age was 43 years, ranging from < 1 month to 84 years; 33% < 18 years. The overall response rate was 79% (95% CI 72–85), with complete responses in 16%. Adverse events were mostly grade 1–2; 13% of patients had a grade 3–4 event related to larotrectinib. Only one patient discontinued due to an adverse event related to larotrectinib.

Conclusions

These data confirm the marked tissue-agnostic efficacy and long durability of response in patients with TRK fusion cancer treated with larotrectinib. Larotrectinib demonstrated a favorable long-term safety profile. Screening patients for NTRK gene fusions should be considered.

Clinical trial identification

NCT02122913, NCT02637687, NCT02576431.

Legal entity responsible for the study

Bayer.

Funding

Bayer.

Disclosure

F. Doz: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (self): Celgene; Advisory / Consultancy: Bayer; Advisory / Consultancy: Loxo Oncology; Advisory / Consultancy: Servier. L. Mascarenhas: Speaker Bureau / Expert testimony: Bayer. J. Berlin: Research grant / Funding (institution): PsiOxus; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): AbbVie (pharamcyclics); Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): FivePrime; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Macrogenics; Honoraria (self): Nestle; Advisory / Consultancy: Rafeal; Advisory / Consultancy: Seattle Genetics; Honoraria (self): Eisai; Advisory / Consultancy: Taiho; Advisory / Consultancy: Armo. All other authors have declared no conflicts of interest.

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Poster display session Poster Display

142P - Relation between Interleukin -4 (590C/T) gene polymorphism and hepatocellular carcinoma risk in HBV and HCV patients

Presentation Number
142P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Suzy F. Gohar
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Suzy F. Gohar
  • Belal Montaser
  • Naglaa Elabd
  • Moamena Elhamoly
  • Amany Saleh
  • Eman Salem
  • Ghada Abo-Zeid
  • Mahmoud Rizk

Abstract

Background

Interleukin-4 (IL-4) is an important modulator in the immune response of macrophages, B and T cells to stand in front of infections and malignancy. This study aimed to assess the association between IL-4 gene 590CT polymorphism and risk of hepatocellular carcinoma (HCC) on top of viral hepatitis.

Methods

This study was conducted on 220 patients and 60 apparently healthy individuals. One hundred and twenty patients with HCV infection (group 1) classified as sixty patients with liver cirrhosis and sixty with HCC, one hundred patients with HBV infection (group 2) classified as fifty with liver cirrhosis and fifty with HCC. Virus status of the patients was confirmed by measuring HBsAg, HCV antibodies and real time PCR. Liver cirrhosis was assessed by laboratory investigations, abdomino-pelvic ultrasound and CHILD score. Patients with HCC were diagnosed by triphasic CT, alphafeto-protein level (AFP) and biopsy. The studied groups were genotyped for IL-4 590C/T gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

IL-4 590C/T gene analysis detected significant variation between studied groups, regarding genotype and allele frequencies (p = 0.025 and p = 0.002 respectively). There were higher frequencies of CC genotype and C allele in HCC and cirrhotic hepatitis C patients than controls. C allele had higher prevalence in HCC than cirrhosis in HBV patients. CT+CC genotype carriers had an elevated HCC risk odd ratio (OR): 4.6 [95% CI: 1.5 –14] and OR 3.6 [95% CI: 1.1 –11.6], in HCV and HBV patients in contrast to controls. C allele was associated with increased cirrhotic and HCC risk in HCV infected patients with OR = 4 [95% CI: 1.8 – 8.8] and OR = 2.3 [95% CI: 1.1 – 5.2] versus control group. In HBV patients C allele showed higher HCC risk with OR = 4.2 [95% CI: 1.8 – 9.5] when compared to controls.

Conclusions

IL-4 590C/T gene polymorphism may have a role in occurrence of HCC on top of liver cirrhosis.

Legal entity responsible for the study

authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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To use or not to use: Genomics assays in guiding adjuvant treatment of HR positive breast cancer Challenge Your Expert session

To use or not to use: Genomics assays in guiding adjuvant treatment of HR positive breast cancer

Lecture Time
08:00 AM - 08:15 AM
Speakers
  • Fatima Cardoso
Location
Hall 407, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
08:00 AM - 08:45 AM
Authors
  • Fatima Cardoso
Mini Oral session - Breast cancer Mini Oral session

LBA5 - The role of radiation therapy in clinically node-positive, pathological negative nodes after neoadjuvant chemotherapy in breast cancer patients: In sentinel node biopsy and trastuzumab era

Presentation Number
LBA5
Lecture Time
02:30 PM - 02:35 PM
Speakers
  • Ji Hyeon Joo
Location
Hall 405, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 03:40 PM
Authors
  • Ji Hyeon Joo
  • Yongkan Ki
  • Su Ssan Kim

Abstract

Background

Although current guidelines recommend deciding on postmastectomy radiation therapy (PMRT) or regional nodal irradiation (RNI) after breast conserving surgery (BCS) depending on initial clinical stages before neoadjuvant chemotherapy (NAC), it is controversial whether adjuvant radiation therapy (RT) can be omitted for patients with excellent response. This retrospective study evaluates if PMRT or RNI after BCS significantly reduces locoregional recurrence rate in patients with clinically positive, pathologic negative lymph nodes (LNs) after NAC.

Methods

From 1999 to 2016, 1831 women with breast cancer underwent NAC and surgery. Of them, 427 patients with clinically node-positive and pN0 disease were analyzed.

Results

Median follow-up was 65.4 months. The 5-year locoregional relapse (LRRFS) and disease-free survival (DFS) rates were 96.9% and 88.3%, respectively. In patients with an initial nodal stage of cN2-3, RT significantly reduced LRR, with a hazard ratio (HR) of 0.132 (p = 0.009). However, RT was not shown to be effective in the cN1 group (HR = 0.893, p = 0.9). RT did not improve DFS, regardless of cN stage. PMRT/RNI was defined as the combined set of patients who received PMRT or received RT, including regional nodal irradiation (RNI) after BCS; the effects of PMRT/RNI were analyzed. PMRT/RNI significantly reduced LRR in the cN2-3 patient group (HR = 0.175, p = 0.03), but there was no significant effect for cN1 disease. Among 173 patients who underwent mastectomy, there were 108 and 65 patients, respectively, who received RT or no RT. Among all patients, PMRT had no effect on LRR (p = 0.7). However, among cN2-3 patients, PMRT significantly lowered LRR (HR = 0.10, p = 0.02), while there was no significant effect in cN1 patients.

Conclusions

In analysis of all patients and of mastectomy patients, RT consistently improved local control rate in the cN2 and higher patient group. Similar results were obtained in the combined analysis of PMRT and RNI after BCS. Therefore, in ypN0 patients graded cN2 or higher, RT including RNI is predicted to be absolutely necessary. No conclusion could be reached for cN1 disease.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session Poster Display

410P - Treatment patterns and outcomes of elderly patients with metastatic soft tissue sarcomas (mSTS)

Presentation Number
410P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Yu-ju Kuo
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Yu-ju Kuo
  • Tom Wei-Wu Chen
  • Hsing-Wu Chen
  • Che-Yu Hsu
  • Wei-Hsin Lin
  • Pei-Ming Huang
  • Jen-Chieh Lee
  • Ho-Min Chen
  • Kuo-How Huang
  • Ching- Yao Yang
  • Chih-Chi Chang
  • Rong-Sen Yang
  • Ruey-Long Hong

Abstract

Background

Elderly STS patients (pts) have different clinicopathological feature and health status compared to younger pts. The optimal management for mSTS remained unclear.

Methods

From January 2011 to December 2017, mSTS pts in National Taiwan University Hospital and ≥65-years-old at the time of metastatic disease diagnosis were included. The clinicopathological features and the chemotherapy (C/T) received were collected.

Results

61 mSTS pts ≥65 y/o were identified; the median age was 74 (range 65- 89); male: female 46%: 54%. The most common histologies were liposarcoma (23%), angiosarcoma (19.7%), and sarcoma NOS (18%). 50 (82%) pts received at least one-line of C/T and the median lines of C/T received was 1 (range 1-5). Anthracycline (exclusive of liposomal doxorubicin (lip-dox)) and ifosfamide were administered to 16 (32%) and 8 (16%) pts; 16 (32%) pts received combination chemotherapy as first-line systemic treatment (tx). Another 9 (18%) and 6 (12%) of patients received lip-dox and oral cyclophosphamide (o-cyclo), as first-line systemic tx. With a median follow-up time of 6.8 months (mos), the median OS was 9.57 mos (95% CI 6.03-22.87 mos); pts who received at least one line of C/T had a numerically but not statistically significant better OS as compared to those who did not receive any C/T (17.50 vs 6.83 mos, p = 0.25). The benefit of systemic C/T were similar for pts aged 65-74 vs ≥ 75 (p for interaction = 0.72). In terms of tx efficacy, the PFS and 1-year OS rate of first-line lip-dox, o-cyclo, and doxorubicin were 7.37 mos and 42%; 16.29 mos and 83%, and 6.97 mos and 40%, respectively. The histologies of mSTS pts who received o-cyclo and lip-dox tx are shown in the table. In multivariate Cox model, only liposarcoma histology had a trend for OS impact (HR 0.4, 95% CI 0.15-1.08, p = 0.07).

410P Histology distribution of pts receiving lip-dox and o-cyclo as first-line therapy

HistologyPatient no.Oral cyclophosphamideLiposomal doxorubicin
Angiosarcoma121 (8.33%)4 (33.3%)
Leiomyosarcoma700
Liposarcoma143 (21.43%)1 (7.12%)
Sarcoma NOS1101 (9.09%)
Others172 (11.76%)3 (17.64%)

Conclusions

Systemic C/T should be considered for elderly mSTS pts. Less toxic tx such as o-cyclo or lip-dox could be considered for selective histologies.

Legal entity responsible for the study

The authors.

Funding

Taiwan Maple Orthopedic Association.

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral session - Gynaecological cancers Mini Oral session

228O - Comparison of long-term oncologic outcomes between laparoscopy and laparotomy for stage Ia1-Ib3 cervical cancer: A matched cohort study

Presentation Number
228O
Lecture Time
12:50 PM - 12:55 PM
Speakers
  • Danian Dai
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
12:45 PM - 01:35 PM
Authors
  • Danian Dai
  • He Huang
  • Jihong Liu

Abstract

Background

To compare the long-term oncologic outcome of laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) for patients with stage Ia1-Ib3 cervical cancer.

Methods

A retrospective data of stage Ia1-Ib1 cervical cancer patients who underwent LRH and ARH at Sun Yat-sen University Cancer Center from Jan. 2012 to Dec. 2015 was collected. Patients were re-classified according to the 2018 FIGO staging system for cervical cancer and screened out 679 cases with stage Ia1-Ib3 cervical cancer. Propensity score matching (PSM) was performed by software SPSS 22.0, and a total of 268 patient pairs (LRH-ARH) were enrolled and analyzed. Oncologic outcomes and prognosis factors were compared between patients undergoing LRH vs. ARH.

Results

(1) Baseline characteristics after PSM: There were no statistical differences between LRH and ARH, but only in grade (p = 0.001). (2) Operation related data: The operative time [(228±90) vs (210±54) min], estimated blood loss (EBL) [(129.5±138.2) vs (207.8±204.6) ml], and the length of hospital stay [(10.6±3.5) vs (12.6±3.5) days] in the LRH group were significantly shorter compared with ARH group (all P < 0.001). (3) Recurrence and survival data: There was a significant difference in the 5-year disease-free survival (DFS; 86.4% vs 95.6%, p = 0.002) and 5-year overall survival (OS; 92.2% vs 97.5%, p = 0.017) between the LRH group and ARH groups. (4) Prognosis factors: In univariate and multivariat analysis, the results showed that surgical approach was common independent prognostic factor for OS and DFS. (5) Stratified analysis: Stratified analysis in low-risk patients with cervical cancer showed that, even in stage Ib1 patients with tumor size <2 cm, there were significant differences for OS and DFS between LRH and ARH group (all P < 0.05). Besides, ALR group only showed better DFS than LRH group in patients with no lymph vascular space invasion.

Conclusions

Our results suggest that, for patients with stage Ia1-Ib3 cervical cancer, ARH results in more benefits for OS and DFS compared with LRH. Even in low-risk patients, ARH is still an oncologically safer alternative.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center.

Funding

National Natural Science Fund.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session Poster Display

175P - Hypermethylation of the PCDHB15 promoter predicts the prognosis in gastric cancer

Presentation Number
175P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Yu-ting Lee
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Yu-ting Lee
  • Po-Yen Hsu
  • Yu-Ming Chuang
  • Hongchuan Jin
  • Alfred S. L. Cheng
  • Enders K. W. Ng
  • Chia-Jen Liu
  • Yin-Chen Chen
  • Frank Cheng
  • Michael W. Y. Chan

Abstract

Background

Helicobacter pylori-induced aberrant JAK/STAT3 signaling contributed to the development of gastric cancer. We hypothesize that activated STAT3 may epigenetically repress it’s targets by DNA methylation. The object of this study is to identified the diagnostic and prognostic value of novel STAT3 targets that are hypermethylated in gastric cancer.

Methods

Fifty patients’ clinical data and genomic DNA were collected from the Changhua Christian Hospital, Taiwan. DNA methylation microarray was used to analyze the methylation status in AGS gastric cancer cells and patient samples with different STAT3 status. Bioinformatic analyses was carried out to identify STAT3 targets with differential methylation status. Bisulphite pyrosequencing was designed and performed in cancer and normal tissue to examine the methylation level of the target genes. Receiver operating character (ROC) curve and the survival analysis were examined.

Results

We found that promoter hypomethylation of PCDHB15, a potential STAT3 target, was observed in AGS cells depleted with STAT3, while promoter hypermethylation was observed in patient samples with activated STAT3. Cell line studies found that treatment with the DNMT inhibitor, 5azaDC, restored PCDHB15 expression in AGS. Pyrosequencing in various cell lines, including AGS, MKN28, MKN45, SNU1 and SNU16, demonstrated hypermethylation of the PCDHB15 promoter. Compared to the cancer tissue, a lower PCDHB15 methylation was observed in matched adjacent tissue (P = 0.001) and gastritis tissue (P < 0.001). Interestingly, Kaplain-Meier analysis found that patients with higher PCDHB15 methylation had longer survival as compared to patients with lower methylation (p = 0.03).

Conclusions

Our study indicate that methylated PCDHB15 promoter may be associated with development of gastric cancer. Patients with higher PCDHB15 methylation are prone to have better prognosis.

Legal entity responsible for the study

The authors.

Funding

This study was supported by a grant from Taichung Veterans General Hospital (RVHYCY-107008).

Disclosure

All authors have declared no conflicts of interest.

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Current controversies in the management of primary and secondary liver cancer Multidisciplinary tumour board

The viewpoint of an Interventional radiologist

Lecture Time
01:30 PM - 01:50 PM
Speakers
  • Thierry De Baere
Location
Hall 405, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
12:45 PM - 02:15 PM
Authors
  • Thierry De Baere
Presidential session Proffered Paper session

LBA1 - Brigatinib vs crizotinib in patients with ALK inhibitor-naive advanced ALK+ NSCLC: Updated results from the phase III ALTA-1L trial

Presentation Number
LBA1
Lecture Time
11:00 AM - 11:15 AM
Session Name
Speakers
  • Ross Camidge
Location
Hall 406, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
11:00 AM - 12:30 PM
Authors
  • Ross Camidge
  • Hye Ryun Kim
  • Myung-Ju Ahn
  • James C-H Yang
  • Ji-Youn Han
  • Maximilian J. Hochmair
  • Ki Hyeong Lee
  • Angelo Delmonte
  • Maria Rosario Garcia Campelo
  • Dong-Wan Kim
  • Frank Griesinger
  • Enriqueta Felip
  • Raffaele Califano
  • Alexander Spira
  • Scott Gettinger
  • Marcello Tiseo
  • Quanhong Ni
  • Pingkuan Zhang
  • Sanjay Popat

Abstract

Background

In the first preplanned interim analysis (IA) from ALTA-1L (NCT02737501; median follow-up BRG/CRZ: 11.0/9.3 mo, 99 PFS events), BRG demonstrated superior BIRC-assessed PFS and improved patient-reported quality of life vs CRZ. We report results of the second IA planned at 75% of 198 expected events.

Methods

Patients (pts) with ALK inhibitor–naive advanced ALK+ NSCLC and ECOG PS 0–2 were enrolled. One prior chemotherapy for advanced NSCLC was allowed. Asymptomatic CNS metastases were allowed. Pts were stratified by baseline (BL) brain metastases and prior chemotherapy. All pts had brain MRI at each tumor assessment. Pts were randomized 1:1 to BRG 180 mg QD (with 7-day lead-in at 90 mg) or CRZ 250 mg BID. Pts in the CRZ arm were offered BRG at progression. Primary endpoint: BIRC-assessed PFS (RECIST v1.1). Secondary endpoints included confirmed ORR, confirmed iORR, iPFS by BIRC, OS, and safety.

Results

275 pts were randomized (BRG/CRZ, n = 137/138); median age 58/60 y. 26%/27% received prior chemotherapy; 29%/30% had BL brain metastases. As of 28 Jun 2019, median follow-up was BRG/CRZ: 24.9/15.2 mo, with 150 PFS events. HR of BIRC-assessed PFS was 0.49 (95% CI 0.35–0.68, log-rank P < 0.0001); BRG mPFS was 24.0 mo (95% CI 18.5–NE) vs CRZ 11.0 mo (95% CI 9.2–12.9). Investigator-assessed PFS HR was 0.43 (95% CI 0.31–0.61, median 29.4 vs 9.2 mo). OS was immature (total events: 33/37, BRG/CRZ). In pts with BL brain metastases, the PFS HR was 0.25. Data were less mature in pts without BL brain metastases treated with BRG. Table shows additional efficacy data. Most common TEAEs grade ≥3: BRG: increased CPK (24.3%) and lipase (14.0%), hypertension (11.8%); CRZ: increased ALT (10.2%), AST (6.6%), and lipase (6.6%). Any grade ILD/pneumonitis (BRG/CRZ): 5.1%/2.2%; discontinuations due to AE (BRG/CRZ): 12.5%/8.8%.

Table: LBA1

BIRC-Assessed EfficacyBRGCRZP Value
All pts (ITT), n137138
ORRa , %79 (71–85b)75 (67–82b)0.4376c
Confirmed ORR, %74 (66–81b)62 (53–70b)0.0342c
mDoRd, moNE (19–NEb)14 (9–21b)
PFS events, n (%)63 (46)87 (63)
mPFS, mo24.0 (18.5–NEb)11.0 (9.2–12.9b)
PFS HR0.49 (0.35–0.68b)<0.0001e
Any BL brain metastases, n40f41f
PFS events, n (%)20 (50)30 (73)
PFS HR0.25 (0.14–0.46b)<0.0001e
47g49g
iPFS events, n (%)21 (45)32 (65)
iPFS HR0.31 (0.17–0.56b)<0.0001e
No BL brain metastasesf, n9797
PFS events, n (%)43 (44)57 (59)
PFS HR0.65 (0.44–0.97b)0.0298e
BL measurable brain metastases, n1823
iORRa, %78 (52–94b)30 (13–53b)0.0036c
Confirmed iORR, %78 (52–94b)26 (10–48b)0.0014c
Median iDoRd, moNE (6–NEb)9 (4–9b)

BIRC, blinded independent review committee; DoR, duration of response; iDoR, intracranial DoR; iORR, intracranial ORR; iPFS, intracranial PFS; ITT, intent-to-treat; mDoR, median DoR; NE, not estimable; ORR, objective response rate; PFS, progression-free survival.

Response, ≥1 assessment;

95% CI;

Cochran-Mantel-Haenszel test;

Confirmed responders;

Log-rank;

Per investigator assessment;

Per BIRC assessment.

Conclusions

BRG showed durable PFS superiority vs CRZ in ALK inhibitor–naive ALK+ NSCLC.

Clinical trial identification

NCT02737501.

Editorial acknowledgement

Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Funding

ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Disclosure

R. Camidge: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): Arrys/Kyn; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Clovis; Honoraria (self): Orion; Honoraria (self): Revolution Med; Honoraria (self): Lycera; Honoraria (self): Bio-Thera DSMB; Honoraria (self): Hansoh SRC; Honoraria (self): Daichi Sankyo; Honoraria (self): Ignyta; Honoraria (self): Roche/Genentech; Honoraria (self): Mersana Therapeutics; Honoraria (self): G1 Therapeutics; Honoraria (self): Genoptix. H.R. Kim: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. M. Ahn: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis. J.C. Yang: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche/Genentech/Chugai; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy: Yuhan Pharmaceuticals; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Hansoh Pharmaceuticals. J. Han: Research grant / Funding (self): Roche. M.J. Hochmair: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Takeda; Advisory / Consultancy: Novartis. K.H. Lee: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. A. Delmonte: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. M.R. Garcia Campelo: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ariad; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. F. Griesinger: Advisory / Consultancy: Ariad; Advisory / Consultancy: Takeda; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer. E. Felip: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda; Advisory / Consultancy: Merck. R. Califano: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Novartis. A. Spira: Advisory / Consultancy: Ariad; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. S. Gettinger: Advisory / Consultancy, Research grant / Funding (self): Ariad; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy: Janssen; Research grant / Funding (self): AstraZeneca/MedImmune; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Incyte; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche/Genentech. M. Tiseo: 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: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Otsuka; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. Q. Ni: Full / Part-time employment: Takeda. P. Zhang: Full / Part-time employment: Takeda. S. Popat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Research grant / Funding (institution): Epizyme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: AbbVie.

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Poster display session Poster Display

447P - Hypomagnesaemia: An unnoticed problem in lung cancer patients treated with concurrent chemoradiation

Presentation Number
447P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Sharif Ahmed
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Sharif Ahmed
  • Ashim Kumar Sengupta
  • Md. Rashid Un Nabi
  • Mostafa A. Sumon

Abstract

Background

Hypomagnesaemia is a well-known side-effect in patients receiving cisplatin-containing chemotherapy. However, a small number of patients, who are receiving weekly cisplatin along with radiotherapy, will show symptoms. Till date in Bangladesh no study has been done to find out the incidence of hypomagnesaemia in concurrent chemo-radiotherapy patients.

Methods

This observational study was done between January, 2018 and February, 2019 at the Cancer Care Center of United Hospital Limited, Dhaka, Bangladesh. A total of 100 non-metastatic lung cancer patients were included in this study. Inclusion criteria were: patients treated with concurrent chemo-radiotherapy and weekly cisplatin; no prior chemotherapy; no prior kidney diseases; ECOG PS 1-2. All patients were treated with 40mg/m2 cisplatin weekly with radiotherapy. Radiotherapy doses were range in 60Gy to 70Gy in 2Gy per fraction. During chemotherapy 1000cc 0.9%NaCl saline was used as pre-hydration and post-hydration. Magnesium level was checked at week 1, week 3 and week 6. Events were categorized according common terminology criteria for adverse events v.4.0. In very severe cases IV magnesium was used, and in mild to moderate cases oral supplement has been used.

Results

Among 100 patients, 63 patients suffered various degrees of hypomagnesaemia. 23 patients were symptomatic for hypomagnesaemia and needed IV correction. And 27 patients were suffering from mild hypomagnesaemia. It has been observed that elderly patients suffer more; 41 patients were above the age of 60 years.

Conclusions

Although hypomagnesaemia is rarely symptomatic, it should be kept in mind that severe grade of hypomagnesaemia can cause fatal damage especially in elderly patients. As, Bangladesh is a developing country and accordingly to their food habits, people have low amounts of dietary magnesium as usual. This finding drives us, to change our daily practice to add IV magnesium (2.5mg/5ml) during post-hydration along with 20mmol potassium n weekly cisplatin chemotherapy to prevent hypomagnesaemia. This was a practice changing finding in our canter. To validate this observational finding we need large prospective multicenter 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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Mixed session - Melanoma Mixed Proffered paper and Mini oral session

344O - Metastatic acral melanoma treatment outcomes: A systematic review and meta-analysis

Presentation Number
344O
Lecture Time
03:16 PM - 03:26 PM
Speakers
  • Kenneth K. Cho
Location
Room 324, Singapore, Singapore, Singapore
Date
Sun, 24.11.2019
Time
02:30 PM - 04:00 PM
Authors
  • Kenneth K. Cho
  • Anne E. Cust
  • Yun Megan Foo
  • Guy Eslick

Abstract

Background

Melanomas that typically arise on sun-shielded skin are classified their anatomical location as acral melanoma (AM). These rare melanomas more commonly affect patients of Asian background, and have different aetiological mechanisms and somatic mutation signatures compared to other cutaneous melanomas. The treatment response of systemic therapy for AM is unclear. The current study systematically reviewed and meta-analysed the existing data in the literature regarding the treatment response of AM.

Methods

Five electronic databases were systematically searched from their inception to June 2019, identifying all studies that reported treatment responses of metastatic AM and ALM. Data were independently extracted by two investigators according to predefined clinical endpoints. We used a Random-effects model for data analysis based on event rates (ER) and 95% confidence interval (CI).

Results

Ten studies, with 215 patients, met the inclusion criteria for the meta-analysis. Average complete response probabilities were ER: 9% (95% CI 4%-18%, I2 = 0.00% p < 0.001), partial response ER: 19% (95% CI 12%-29%, I2 = 0.00% p < 0.001), stable disease ER: 35% (95% CI 20%-54%, I2 = 51.94% p = 0.1) and progression of disease ER: 42% (95% CI 26%-59%, I2 = 45.36% p 0.34). Subgroup analysis of patients receiving immunotherapy compared to chronic sun damaged skin and mucosal melanoma will be presented.

Conclusions

Overall patients with metastatic acral melanoma had significant rates of treatment response to systemic 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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