Five-Year Follow-up Confirms Survival Benefit With Nivolumab Plus Chemotherapy in Gastroesophageal Adenocarcinoma
Clinical Summary:
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Design/Population: This 5-year analysis of the phase 3 CheckMate 649 trial evaluated nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment for patients with previously untreated, HER2-negative unresectable or metastatic gastroesophageal adenocarcinoma, with efficacy assessed according to PD-L1 combined positive score.
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Key Outcomes: Nivolumab plus chemotherapy maintained significant improvements in overall and progression-free survival at 5 years compared with chemotherapy alone. Objective response rates and duration of response also remained higher with the combination, with no new safety signals observed during long-term follow-up.
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Clinical Relevance: These findings provide the first 5-year evidence supporting PD-1 inhibitor–based chemotherapy in advanced gastroesophageal adenocarcinoma and reinforce nivolumab plus chemotherapy as a standard first-line treatment for patients with PD-L1–positive disease.
Five-year follow-up from the phase 3 CheckMate 649 trial demonstrated that nivolumab plus chemotherapy continued to improve survival compared with chemotherapy alone in patients with previously untreated, HER2-negative unresectable or metastatic gastroesophageal adenocarcinoma.
In this trial, 1,571 patients were randomized to receive either nivolumab plus chemotherapy (n = 789) or chemotherapy alone (n = 792). The primary end points were overall survival (OS) and progression-free survival (PFS). Key secondary end points included objective response rate (ORR), duration of response, and safety.
After a median follow-up of 60.1 months, nivolumab plus chemotherapy continued to improve both OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.61 to 0.81) and PFS compared with chemotherapy alone among patients with a PD-L1 CPS of at least 5.
The 5-year OS rate was 16% with nivolumab plus chemotherapy compared with 6% with chemotherapy alone. Corresponding 5-year PFS rates were 10% and 6%, respectively. The ORR was 58% with nivolumab plus chemotherapy versus 46% with chemotherapy alone. Median duration of response was 8.5 months and 6.9 months, respectively.
Grade 3/4 treatment-related adverse events occurred in 60% of patients receiving nivolumab plus chemotherapy and 45% of those receiving chemotherapy alone. No new safety signals were identified with extended follow-up.
As study authors concluded, these results “reinforce its use as a standard first-line treatment for PD-L1 positive patients.”
Source:
Janjigian YY, Shitara K, Ajani JA, et al. Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649. Ann Oncol. Published online: February 11, 2026. doi: 10.1016/j.annonc.2026.02.003
