Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649
Y.Y. Janjigian, K. Shitara, J.A. Ajani, L. Shen, M. Dolores Pitarch Garrido, C. Gallardo, L. Wyrwicz, K. Yamaguchi, J. Cleary, E. Elimova, R. Bruges, M. Karamouzis, T. Skoczylas, A. Bragagnoli, T. Liu, M. Tehfe, T. Zander, R. Kowalyszyn, R. Pazo-Cid, M. Schenker, K. Feeny, S. McCraith, N. Hu, M. Lei, J. Zhang, M. Moehler
Abstract
BACKGROUND: We report efficacy and safety results from the CheckMate 649 trial after 5 years of follow-up. PATIENTS AND METHODS: Adults with previously untreated, non-human epidermal growth factor receptor 2-positive, unresectable, advanced or metastatic gastroesophageal adenocarcinoma were randomized to receive nivolumab plus chemotherapy (n = 789) or chemotherapy (n = 792). Primary endpoints were met and reported previously, with nivolumab plus chemotherapy demonstrating superior overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥5. RESULTS: With a minimum follow-up of 60.1 months, the OS benefit [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.61-0.81] and PFS benefit (HR 0.71, 95% CI 0.61-0.82) with nivolumab plus chemotherapy versus chemotherapy in patients with PD-L1 CPS ≥5 were sustained. Five-year OS and PFS rates were 16% versus 6% and 10% versus 6%, respectively. Objective response rate per blinded independent central review was 58% (95% CI 54% to 62%) versus 46% (95% CI 42% to 50%), and median duration of response was 8.5 months (95% CI 7.7-9.9 months) versus 6.9 months (95% CI 5.9-7.6 months), respectively. Survival and response benefits were also maintained in patients with PD-L1 CPS ≥1, patients with PD-L1 CPS ≥10, and all randomized patients. Grade 3/4 treatment-related adverse events occurred in 60% of patients receiving nivolumab plus chemotherapy and 45% of patients receiving chemotherapy. No new safety concerns were observed. CONCLUSIONS: To our knowledge, these are the first reported 5-year results of a programmed cell death protein 1 inhibitor plus chemotherapy in gastroesophageal adenocarcinoma. Nivolumab plus chemotherapy continued to demonstrate long-term survival benefit and acceptable safety after 5 years of follow-up, reinforcing its use as a standard first-line treatment for PD-L1-positive patients.