Nivolumab (NIVO) plus chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 3-year follow-up from CheckMate 649.

Yelena Y. Janjigian Memorial Sloan Kettering Cancer Center, New York, NY info_outline Yelena Y. Janjigian, Kohei Shitara, Markus H. Moehler, Marcelo Garrido, Carlos Gallardo, Lin Shen, Kensei Yamaguchi, Lucjan Wyrwicz, Tomasz Skoczylas, Arinilda Silva Campos Bragagnoli, Tianshu Liu, Mustapha Tehfe, Elena Elimova, Ricardo Elias Bruges Maya, James M. Cleary, Michalis Karamouzis, Samira Soleymani, Ming Lei, Carlos Amaya-Chanaga, Jaffer A. Ajani

Authors Yelena Y. Janjigian Memorial Sloan Kettering Cancer Center, New York, NY info_outline Yelena Y. Janjigian, Kohei Shitara, Markus H. Moehler, Marcelo Garrido, Carlos Gallardo, Lin Shen, Kensei Yamaguchi, Lucjan Wyrwicz, Tomasz Skoczylas, Arinilda Silva Campos Bragagnoli, Tianshu Liu, Mustapha Tehfe, Elena Elimova, Ricardo Elias Bruges Maya, James M. Cleary, Michalis Karamouzis, Samira Soleymani, Ming Lei, Carlos Amaya-Chanaga, Jaffer A. Ajani Organizations Memorial Sloan Kettering Cancer Center, New York, NY, National Cancer Center Hospital East, Kashiwa, Japan, Johannes-Gutenberg University Clinic, Mainz, Germany, Clinica San Carlos de Apoquindo, Pontificia Universidad Católica, Santiago, Chile, Fundacion Arturo López Pérez, Providencia, Chile, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China, The Cancer Institute Hospital of JFCR, Tokyo, Japan, Klinika Onkologii i Radioterapii, Narodowy Instytut Onkologii, Warszawa, Poland, II Klinika Chirurgii Ogólnej, Gastroenterologicznej i Nowotworów Układu Pokarmowego, Medical University of Lublin, Lublin, Poland, Fundacao Pio Xii Hosp Cancer De Barretos, Barretos, Brazil, Zhongshan Hospital, Fudan University, Shanghai, China, Oncology Center– Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada, Princess Margaret Cancer Centre, Toronto, ON, Canada, Instituto Nacional de Cancerologia E.S.E., Bogotá, Colombia, Dana-Farber Cancer Institute, Boston, MA, Laiko General Hospital of Athens, Athens, Greece, Bristol Myers Squibb, Princeton, NJ, The University of Texas MD Anderson Cancer Center, Houston, TX Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Bristol Myers Squibb Background: NIVO + chemo demonstrated superior overall survival (OS) and clinically meaningful progression-free survival (PFS) benefit vs chemo and acceptable safety in previously untreated patients (pts) with advanced GC/GEJC/EAC, leading to approvals in multiple countries including the US. NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy after 2 years of follow-up. We present efficacy and safety analyses from NIVO + chemo vs chemo from the 3-year follow-up of CheckMate 649. Methods: Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression, excluding pts with known HER2-positive status. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) ≥ 5. Results: 1581 pts were concurrently randomized to NIVO + chemo or chemo. With 36-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS ≥ 5 and all randomized pts. The objective response rate (ORR) per BICR in pts with PD-L1 CPS ≥ 5 who had measurable lesions at baseline was 60% (95% CI 55–65) with NIVO + chemo vs 45% (95% CI 40–50) with chemo; in all randomized pts, ORR per BICR was 58% (95% CI 54–62) with NIVO + chemo vs 46% (95% CI 42–50) with chemo. Responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS ≥ 5 (median [m] duration of response [mDOR] 9.6 mo [95% CI 8.2–12.4] vs 7.0 mo [95% CI 5.6–7.9], respectively) and in all randomized pts (mDOR 8.5 mo [95% CI 7.7–9.9] vs 6.9 mo [95% CI 5.8–7.2], respectively). OS benefit with NIVO + chemo was observed across most prespecified subgroups. No new safety signals were identified. A summary of treatment-related adverse events (TRAEs) is shown in the Table. Additional analyses will be presented. Conclusions: After 3 years of follow-up, NIVO + chemo continued to demonstrate clinically meaningful long-term survival benefit with acceptable safety, further supporting its use as a standard 1L treatment in previously untreated pts with advanced GC/GEJC/EAC. Clinical trial information: NCT02872116. Efficacy PD-L1 CPS ≥ 5 All randomized NIVO + chemo (n = 473) Chemo (n = 482) NIVO + chemo (n = 789) Chemo (n = 792) mOS (95% CI), mo 14.4 (13.1–16.2) 11.1 (10.0–12.1) 13.7 (12.4–14.5) 11.6 (10.9–12.5) HR (95% CI) 0.70 (0.61–0.81) 0.79 (0.71–0.88) mPFS a (95% CI), mo 8.3 (7.0–9.3) 6.1 (5.6–6.9) 7.7 (7.1–8.6) 6.9 (6.7–7.2) HR (95% CI) 0.70 (0.60–0.81) 0.79 (0.71–0.89) Safety, all treated pts, n (%) NIVO + chemo (n = 782) Chemo (n = 767) Any-grade TRAEs 739 (95) 682 (89) Grade 3/4 473 (60) 346 (45) Leading to discontinuation 331 (42) 198 (26) a per BICR.

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