1905 - A phase 3 study of nivolumab (Nivo) in previously treated advanced gastric or gastric esophageal junction (G/GEJ) cancer (ATTRACTION-2): Two-years update data.

Background

Nivo monotherapy has shown superior efficacy with manageable safety for G/GEJ cancer refractory to, or intolerant of standard chemotherapy in a phase 3 study (ATTRACTION-2). Here, we report 2-year updated results of survival.

Methods

A total of 493 patients with unresectable advanced or recurrent G/GEJ cancer after failure of two or more previous chemotherapy regimens were randomized in a 2:1 ratio to receive 3 mg/kg Nivo (N = 330) or placebo (N = 163) until progressive disease or unacceptable toxicity. The primary endpoint was overall survival (OS). Updated results of the efficacy and safety were based on ≥ 2-year follow-up after last patient enrollment. As a subgroup analysis, the OS data by BOR was evaluated.

Results

As of data cut-off on February 2018, 2 years after last patient enrollment, the median OS (mOS) was 5.3 months with Nivo versus 4.1 months with placebo (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51-0.76). The OS rates of Nivo and Placebo were 27.3% and 11.6% at 12 months, and 10.6% and 3.2% at 24 months, respectively. In a OS subgroup analysis stratified by BOR, mOS in PR patients in Nivo arm was not reached. Median OS in SD patients were 9.4 and 7.6 months (HR 0.70, 95%CI 0.44-1.09), and mOS in PD patients were 3.8 and 3.8 months (HR 0.86, 5%CI 0.64-1.16) in Nivo and placebo arm, respectively. In addition, 12-month OS rate in PR patients was 86.7% in Nivo arm. OS rate at 12 months in SD patients were 36.9 and 24.2%, and OS rate at 12 months in PD patients were 12.4 and 6.9% in Nivo and placebo arm, respectively. The safety analysis for 2-year follow-up will be presented.

Conclusions

Nivo has significantly improved OS with 2-year follow-up. In PR and SD patients, the subgroup analysis of OS favored Nivo over placebo.

Clinical trial identification

NCT02267343. Other Study ID Numbers: ONO-4538-12.

Legal entity responsible for the study

Ono Pharmaceutical Co., Ltd.

Funding

Ono Pharmaceutical Co., Ltd and Bristol-Myers Squibb.

Editorial Acknowledgement

We thank Naokazu Gion for providing statistical support, the project leader Mitsunobu Tanimoto (ONO Pharmaceutical,.CO.LTD.).

Disclosure

T. Satoh: Consulting fees: Chugai, Ono, Taiho, Eli Lilly, Daiichi Sankyo; Honoraria: Chugai, Ono, Yakult Honsha, Bristol-Myers Squibb, Merck Serono, Taiho, Eli Lilly, Daiichi Sankyo; Departmental research grants: Chugai, Ono, Yakult Honsha. L-T. Chen: Advisory board role: Ono, BMS, MSD, Eli Lilly, PhamaEngine, Five Prime, Novartis, AstraZeneca; Honoraria: Ono, BMS, MSD, Eli Lilly, PhamaEngine, TTY, SyncoreBio, Five Prime, Novartis, AstraZeneca, Ipsen; Research funds: Novartis, Pfizer, Merck Serono, Polaris, TTY, SyncoreBio, Celgene. Y-K. Kang: Personal fees: Ono Pharmaceutical. Co., Ltd., Bristol-Myers Squibb, Lilly / ImClone, Taiho Pharmaceutical, Novartis, Roche / Genentech, Bayer; Grants: Roche / Genentech, Novartis, Bayer. K. Kato: Research funds: Ono Pharmaceutics, Merck and Co. Shionogi, Merck Serono. H.C. Chung: Consultation honoraria: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono; Research funds: Lilly, GSK, MSD, Merck-Serono, BMS-Ono, Taiho; Speaker\'s bureau: Merck-Serono, Lilly, Foundation-Medicine. J-S. Chen: Research funds: Ono/BMS, MSD, Ill Lilly, Roche; Speaker\'s bureau: Ono/BMS, MSD, Ill Lilly, TTY Biopharm, Novartis. K. Muro: Honoraria: Ono, Chugai, Bayer, Takeda, Taiho and Eli Lilly; Research funds: MSD, Ono, Daiichi Sankyo, Shionogi, Kyowa Hakko Kirin, Gilead Science. T. Yoshikawa: Honoraria: Ono, Bristol, Lilly, Chugai, Taiho, Yakult, MSD, Abbott, Takeda, Daiichi-Sankyo, Nihon-Kayaku, Kaken-Seiyaku, Olympus, Johnson and Johnson, and Covidien; Research funds: Chugai, Taiho, Yakult, Novartis. T. Tamura: Research funds: Ono, Bristol-Myers Squibb. K-W. Lee: Research funds: Ono Pharmaceutical (to institution). N. Boku: Honoraria: Ono, Bristol-Myers Squibb; Research funds: Ono, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.