Nivolumab Plus Chemotherapy Maintains Survival Advantage in Gastroesophageal Adenocarcinoma

Key Clinical Takeaways:

• Design/Population: CheckMate 649 randomized patients with previously untreated, non–HER2-positive advanced or metastatic gastroesophageal adenocarcinoma to nivolumab plus chemotherapy or chemotherapy alone. Five-year outcomes were evaluated in patients with PD-L1 CPS ≥5 and across broader PD-L1 subgroups.
• Key Outcomes: Nivolumab plus chemotherapy sustained significant improvements in overall and progression-free survival at 5 years, with higher objective response rates and longer duration of response. Grade 3/4 adverse events were more frequent with nivolumab plus chemotherapy, but no new safety concerns emerged.
• Clinical Relevance: These long-term data provide the first 5-year evidence supporting PD-1 inhibitor-based chemotherapy in gastroesophageal adenocarcinoma. The findings reinforce nivolumab plus chemotherapy as a standard first-line option for patients with PD-L1–positive disease.

Long-term follow-up results from the phase 3 CheckMate 649 trial demonstrate that adding nivolumab to chemotherapy continues to prolong survival compared with chemotherapy alone among previously untreated patients with non-HER2-positive, unresectable or metastatic gastroesophageal adenocarcinoma.

These results build on previously reported data showing superior overall survival (OS) and progression-free survival (PFS) with the combination vs chemotherapy alone for patients with a PD-L1 combined positive score (CPS) ≥5.

In this study, 1571 patients were randomized to receive either nivolumab plus chemotherapy (n = 789) or chemotherapy alone (n = 792). Primary end points included OS and PFS. Key secondary end points were objective response rate (ORR), duration of response, and safety.

At a median follow-up of 60.1 months, nivolumab plus chemotherapy demonstrated sustained benefit in both OS (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.61 to 0.81) and PFS (HR, 0.71; 95% CI, 0.61 to 0.82) in patients with PD-L1 CPS ≥5.

The 5-year OS rate was 16% in the nivolumab plus chemotherapy arm and 6% in the chemotherapy arm, with corresponding 5-year PFS rates of 10% and 6%, respectively. The ORR was 58% (95% CI, 54 to 62) in nivolumab plus chemotherapy and 46% (95% CI, 42 to 50) in the chemotherapy, and median duration of response was 8.5 months (95% CI, 7.7 to 9.9) and 6.9 months (95% CI, 5.9 to 7.6), respectively. 

Regarding safety, grade 3/4 treatment-related adverse events were reported in 60% of patients in the nivolumab plus chemotherapy arm and 45% of patients in the chemotherapy arm. However, no new safety signals were identified.

As study authors concluded, “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.”

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