Correlation of tumor mutation with efficacy in patients with gastric cancer who received nivolumab and ramucirumab combination therapy.

Authors

null

Izuma Nakayama

Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

Izuma Nakayama , Hirokazu Shoji , Hiroki Hara , Taito Esaki , Nozomu Machida , Kengo Nagashima , Kazunori Aoki , Kazufumi Honda , Daisuke Takahari , Takahiro Miyamoto , Narikazu Boku , Ken Kato

Organizations

Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, Saitama Cancer Center, Saitama, Japan, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan, Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan, Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan, Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan, Department of Cancer Chemotherapy Center, Osaka Medical Collage Hospital, Osaka, Japan, National Cancer Center Hospital, Tokyo, Japan

Research Funding

Pharmaceutical/Biotech Company
Ono Pharmaceutical Co. Ltd

Background: Nivolumab (Nivo) plus ramucirumab (Ram) showed promising efficacy in the second-line chemotherapy for advanced gastric cancer (AGC) in NIVORAM study with the 44% of objective response rate (ORR) and 38.6% of 6-month progression free survival (PFS) rate. We investigated the correlation of tumor mutation load and efficacy. Methods: Patients received Nivo (3mg/kg, Q2W) in combination with Ram (8mg/kg, Q2W) until unacceptable toxicity or disease progression. Tissue samples were collected before the treatment, and analyzed for tumor mutation load using Oncomine Tumor Mutation Load Assay. Efficacy included ORR, overall survival (OS), PFS and duration of response. OS and PFS curves were estimated using the Kaplan-Meier method. Hazard ratio (HR) was estimated using the Cox proportional hazards model. Results: By the data cut off of December 15, 2018, the median follow duration on therapy was 13.7 month. Thirty AGC pts who obtained tissue sample were analyzed. Median tumor mutation load (TML) was 6.755 mutation/Mb (range 0.84-19.67). Higher TML (cut-off median) related to better tendency of efficacy with ORR (40.0% vs 20.0%), PFS (5.32 vs 2.33 months) and OS (18.1 vs 10.6 months). 6-month PFS rate was better in TML higher group (48%) compared to TML lower group (18%). In multivariate analysis, higher TML showed 2.030 of hazard ratio (95% CI; 0.849-4.855, p-0.112) for PFS, and 1.915 (95% CI; 0.578-6.343, p=0.287) for OS. Conclusions: The patients with higher tumor mutation load have a better tendency for OS and PFS, among AGC patients who received Nivo and Ram combination therapy. Clinical trial information: NCT02999295

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Abstract Details

Meeting

2020 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Esophageal and Gastric Cancer and Other GI Cancers

Track

Esophageal and Gastric Cancer,Other GI Cancer

Sub Track

Translational Research

Clinical Trial Registration Number

NCT02999295

Citation

J Clin Oncol 38, 2020 (suppl 4; abstr 413)

Abstract #

413

Poster Bd #

G2

Abstract Disclosures