Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649
Mené sur 1 581 patients atteints d'un adénocarcinome gastro-oesophagien non résécable, de stade avancé ou métastatique, cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale à 5 ans, et la toxicité de l'ajout de nivolumab à une chimiothérapie de première ligne, en fonction du niveau d'expression tumorale de PD-L1
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-HER2+, 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 PD-L1 combined positive score (CPS) ≥5.
Results: With minimum follow-up of 60.1 months, the OS benefit (hazard ratio [HR] 0.71 [95% 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 54-62) versus 46% (95% CI 42-50), and median duration of response was 8.5 (95% CI 7.7-9.9) months versus 6.9 (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 TRAEs 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 PD-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.
Annals of Oncology , résumé, 2026