Standard 1L chemo options for advanced or metastatic HER2-negative GC/GEJC result in poor overall survival (OS; median < 1 year). CheckMate 649 is the largest randomized, global phase III study of programmed death (PD)-1 inhibitor-based therapies in 1L GC/GEJC/EAC. We report OS at a pre-specified interim analysis and progression-free survival (PFS) at final analysis from the NIVO + chemo vs chemo arms in patients (pts) whose tumors expressed PD-ligand 1 (L1) combined positive score (CPS) ≥ 5.
Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of PD-L1 expression. Pts with known HER2-positive status were excluded. Pts were randomized to receive NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review, in pts whose tumors expressed PD-L1 CPS ≥ 5.
1581 pts were concurrently randomized in nivo+chemo and chemo arms, including 955 pts (60%) with PD-L1 CPS ≥ 5. With a minimum follow-up of 12 months (mo), NIVO + chemo showed a statistically significant improvement in OS and PFS vs chemo in pts whose tumors expressed PD-L1 CPS ≥ 5 (OS, HR 0.71 [98.4% CI 0.59–0.86;
Efficacy NIVO + chemo Chemo PD-L1 CPS ≥ 5 N = 473 N = 482 14.4 (13.1–16.2) 11.1 (10.0-12.1) HR (98.4% CI; 0.71 (0.59-0.86; 7.7 (7.0-9.2) 6.1 (5.6-6.9) HR (98.0% CI; 0.68 (0.56-0.81; 14.0 (12.6-15.0) 11.3 (10.6-12.3) HR (99.3% CI; 0.77 (0.64–0.92; 13.8 (12.6–14.6) 11.6 (10.9-12.5) HR (99.3% CI; 0.80 (0.68-0.94; Any grade 444 (95) 407 (88) Grade 3-4 277 (59) 203 (44) Leading to discontinuation 178 (38) 115 (25) Deaths 8 (2) 4 (<1)
NIVO is the first PD-1 inhibitor to demonstrate superior OS and PFS in combination with chemo vs chemo alone in previously untreated pts with advanced GC/GEJC/EAC, with a manageable safety profile. NIVO + chemo represents a potential new standard 1L treatment option for these pts.
NCT02872116.
Writing and editorial assistance was provided by Tanmayi Mankame, PhD, of Parexel International, funded by Bristol-Myers Squibb Company.
Bristol-Myers Squibb Company.
Bristol-Myers Squibb Company.
M. Moehler: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Adboards: Bristol Myers Squibb. K. Shitara: Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly and Company; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Takeda Pharmaceuticals; Advisory/Consultancy: Pfizer Inc; Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie Inc; Honoraria (self): Yakult; Research grant/Funding (institution): Dainippon Sumitomo Pharma; Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Chugai Pharma; Advisory/Consultancy, Research grant/Funding (institution): Merck Pharmaceutical; Research grant/Funding (institution): Medi Science; Advisory/Consultancy: GlaxoSmithKline. M. Garrido: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Roche. K. Yamaguchi: Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Chugai; Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Daiichi-Sankyo; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Ono; Advisory/Consultancy, Research grant/Funding (institution): Yakult Honsha; Advisory/Consultancy: Takeda; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Merck Serono. M. Schenker: Research grant/Funding (self), fee for clinical research activity: Bristol Myers Squibb; Research grant/Funding (self), fee for clinical research activity: Roche; Research grant/Funding (self), fee for clinical research activity: Pfizer; Research grant/Funding (self), fee for clinical research activity: MSD; Research grant/Funding (self), fee for clinical research activity: Eli Lilly; Research grant/Funding (self), fee for clinical research activity: Novartis; Research grant/Funding (self), fee for clinical research activity: Astellas; Research grant/Funding (self), fee for clinical research activity: GSK; Research grant/Funding (self), fee for clinical research activity: AstraZeneca; Research grant/Funding (self), fee for clinical research activity: Merck Serono; Research grant/Funding (self), fee for clinical research activity: Regeneron. M. Tehfe: Advisory/Consultancy: Bristol Myers Squibb. V. Poulart: Full/Part-time employment: Bristol Myers Squibb. D. Cullen: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. M. Lei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. K. Kondo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Bristol Myers Squibb. M. Li: Full/Part-time employment: Bristol Myers Squibb. J.A. Ajani: Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb. Y.Y. Janjigian: Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Speaker Bureau/Expert testimony: ASCO; Advisory/Consultancy: Michael J. Hennessy Associates; Advisory/Consultancy: Paradigm Medical Communications, LLC; Advisory/Consultancy: Zymeworks Inc.; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Seattle Genetics; Shareholder/Stockholder/Stock options: Rgenix; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Ono Pharma; Advisory/Consultancy, Research grant/Funding (institution): Merck & Co Inc.; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Imugene. All other authors have declared no conflicts of interest.