Browsing Over 783 Presentations
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)
- Rosita Y. Purwanto (Yogyakarta, Indonesia)
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.
230P - Molecular profiling and clinical characteristics of Chinese patients with prostate cancer (ID 830)
- Ranlu Liu (Tianjin, China)
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.
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)
- Chunwei Xu (Fuzhou, China)
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.
35P - Pathological response to weekly nabpaclitaxel and carboplatin followed by anthracycline regimen in triple negative breast cancer (ID 959)
- Goteti Sharat Chandra (New Delhi, India)
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.
437P - Long-term efficacy and toxicity outcome of adjuvant external beam radiotherapy for medullary thyroid cancer: A single institution cohort study (ID 986)
- Ka Man Cheung (Kowloon, Hong Kong PRC)
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.
417P - Efficacy and safety of lorlatinib in subsequent lines of therapy in ALK and ROS1 positive lung cancer (ID 1008)
- Amit Kumar (Mumbai, India)
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.
Genitourinary tumours, prostate (ID 1148)
76P - Targeted tumour photoImmunotherapy against triple-negative breast cancer therapy (ID 154)
- Vivek Raju (Coimbatore, India)
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.
343P - Head-to-head comparison of palonosetron versus granisetron for prevention of chemotherapy induced nausea and vomiting: Systematic review and meta-analysis (ID 183)
- Chin-Yu Hsu (Taipei City, Taiwan)
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.
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)
- Elizabeth Marcella (Tangerang, Indonesia)
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.
158P - A phase II study of trastuzumab with S-1 plus oxaliplatin for HER2-positive advanced gastric cancer (HIGHSOX study): Final report (ID 275)
- Atsuo Takashima (Tokyo, Japan)
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.
113TiP - Prospective observational study monitoring circulating tumour DNA in resectable colorectal cancer patients undergoing radical surgery: GALAXY study in CIRCULATE-Japan (ID 328)
- Hiroki Yukami (Kashiwa, Japan)
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.