First-line nivolumab plus chemotherapy for advanced gastroesophageal adenocarcinoma: 5-year follow-up of CheckMate 649

The multinational phase 3 CheckMate 649 trial evaluated addition of nivolumab to first-line chemotherapy for non-HER2+, unresectable, advanced or metastatic gastroesophageal adenocarcinoma. Patients were randomized to nivolumab plus chemotherapy (n=789) or chemotherapy alone (n=792). Primary analysis showed superior overall survival (OS) and progression-free survival (PFS) with addition of nivolumab in patients with PD-L1 combined positive score (CPS) ≥ 5. Five-year follow-up results of the trial have now been published. With a minimum follow-up of 60.1 months, 5-year OS and PFS rates among patients with CPS ≥ 5 were 16% versus 6% and 10% versus 6%, respectively, with nivolumab plus chemotherapy versus chemotherapy alone; objective response rate per blinded independent central revies was 58% versus 46%, and median duration of response was 8.5 versus 6.9 months. 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 or 4 treatment-related adverse events occurred in 60% of patients receiving nivolumab plus chemotherapy and 45% of patients receiving chemotherapy. The authors conclude that nivolumab plus chemotherapy continued to demonstrate long-term survival benefit and acceptable safety at 5 years of follow-up.