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First-line nivolumab (NIVO) plus chemotherapy (chemo) vs chemo in patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): CheckMate 649 Chinese subgroup analysis 2-year follow-up
Background
NIVO + chemo demonstrated a clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) vs chemotherapy alone, along with acceptable safety, in a preplanned analysis of previously untreated Chinese patients from CheckMate 649 after 12 months of follow-up. Results were consistent with those for the overall study population with advanced GC/GEJC/EAC. Based on data from CheckMate 649, NIVO + chemo was approved as first-line treatment for advanced GC/GEJC/EAC in China and other countries. 2-year follow-up data for Chinese patients in CheckMate 649 is reported.
Methods
Adults with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of programmed death ligand 1 (PD-L1) expression. Patients with known HER2-positive status were excluded. Patients 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 patients with PD-L1 combined positive score (CPS) ≥ 5.
Results
208 Chinese patients were concurrently randomized to NIVO + chemo (n = 99) or chemo (n = 106), including 156 (75%) with PD-L1 CPS ≥ 5; 88% had GC, 12% had GEJC, and no patients had EAC. At 25 months of minimum follow up, NIVO + chemo continued to show clinically meaningful improvement in OS with median OS (95% CI) in patients with PD-L1 CPS > 5 of 15.5 months (11.9-21.1) for NIVO + chemo vs 9.6 months (8.0-12.1) for chemo (HR 0.56 [95% CI 0.38-0.81]); in all randomized patients the median OS (95% CI) was 14.3 months (11.5-16.5) for NIVO + chemo vs 10.3 months (8.1-12.1) for chemo (HR 0.63 [95% CI 0.46-0.86]). The median PFS (95% CI) in patients with PD-L1 CPS ≥ 5 was 8.5 months (6.0-14.0) for NIVO + chemo vs 4.3 months (4.1-6.5) for chemo (HR 0.51 [95% CI 0.34-0.76]); in all randomized patients, the median PFS was 8.3 months (6.2-12.4) for NIVO + chemo vs 5.6 months (4.2-6.8) for chemo (HR 0.57 [95% CI 0.41-0.80]). Objective response rate (ORR) in patients with PD-L1 CPS ≥ 5 was 68% vs 48% and median duration of response (DOR) was 12.5 months vs 6.9 months for NIVO + chemo vs chemo, respectively; ORR in all randomized patients was 66% vs 45% and median DOR was 12.5 months vs 5.6 months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 66% and 50% of patients with NIVO + chemo vs chemo, and any-grade TRAEs leading to discontinuation were observed in 49% and 26% of patients, respectively.
Conclusions
NIVO + chemo continued to demonstrate clinically meaningful improvement in OS, PFS, and ORR and have a longer DOR vs chemo alone in previously untreated Chinese patients, along with acceptable safety. These results are consistent with those observed in the overall study population with advanced GC/GEJC/EAC from CheckMate 649.
Clinical trial identification
NCT02872116.
Editorial acknowledgement
All authors contributed to and approved the abstract, writing and editoiral assistance was provided by Rajendra Damle, PhD, of Parexel International, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
The study was supported by Bristol Myers Squibb.
Disclosures
L. Shen: Advisory / Consultancy: BMS/AstraZeneca/BI/MSD/Daiichi Sankyo/Roche; Research grant / Funding (institution): Yaojie Ankang (Nanjing) Technology Co., Ltd./QiLu Pharmaceutical, Baiji Shenzhou (Beijing) Biotechnology Co., Ltd/Zaiding Pharmaceutical, Beijing Xiantong Biomedical Technology Co., Ltd. C. Amaya Chanaga: Full / Part-time employment: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
