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
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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