First-Line Nivolumab Plus Chemo for Patients With Advanced or Metastatic Gastric Cancer

Key Clinical Summary: 

• Design/Population: Phase 3 CheckMate 649 study evaluating first-line nivolumab plus chemotherapy versus chemotherapy alone in patients with unresectable, advanced or metastatic gastric, gastroesophageal junction, and esophageal adenocarcinomas.
• Key Outcomes: At 5-year follow-up, nivolumab plus chemotherapy continued to demonstrate long-term survival benefit, with improvements in overall survival, progression-free survival, and overall response rate. Benefit was observed across PD-L1 CPS subgroups and enriched at higher CPS levels, with no new safety signals.
• Clinical Relevance: First-line nivolumab plus chemotherapy provides durable efficacy with an acceptable safety profile, supporting its use as a standard treatment option and demonstrating that long-term survival is achievable in metastatic disease.

Yelena Janjigian, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses 5-year follow-up results from the CheckMate 649 study assessing first-line nivolumab plus chemotherapy in patients with unresectable, advanced or metastatic gastric, gastroesophageal junction, and esophageal adenocarcinomas.

Results demonstrated that this combination continued to show long-term efficacy and safety, strengthening its role as a first-line option in this patient population.

Transcript: 

Hello, my name is Dr Yelena Janjigian. I'm a medical oncologist and chief of GI oncology service at Memorial Sloan Kettering Cancer Center in New York City and I'm really excited to share that the 5-year survival follow-up results from CheckMate 649 study are now published in Annals of Oncology.

As you recall, CheckMate 649 is a large phase 3 study that brought immune checkpoint blockade with nivolumab to our patients with metastatic disease for patients with adenocarcinoma of G-junction and stomach. Patients were randomized to receive chemotherapy with FOLFOX versus FOLFOX and nivolumab, and for the first time to be able to report 5-year survival rates in stage 4 disease is quite really satisfying but also very emotional because up to this point, many studies really quoted dismal survival rates in our disease for patients with stage 4 adenocarcinoma with median overall survival of being well under 1 year.

It's a pleasure to share the updated results and after 5 years of follow-up in a stage 4, large phase 3 global study, first-line nivolumab plus chemotherapy continued to show efficacy and long-term survival benefit. Overall and progression-free survival benefit was observed across all assessed PD-L1 CPS subgroups and enriched at higher PD-L1 CPS cutoffs. We also saw improvement in overall response rate in first-line setting, which is quite meaningful for our patients who are presenting with a large disease burden and need tumor shrinkage to improve their quality of life. 

Safety of nivolumab plus chemotherapy was acceptable and no new safety signals were observed. Really looking at long-term survival rates, we're seeing that it's really attainable and I quote these numbers, this data, to our patients that gives them hope that even with metastatic disease they can be alive and well 5 years later. 

It's a pleasure to be able to share this data with you, it's now online at Annals of Oncology so please feel free to check it out. We continue to improve outcomes for our patients, of course, now with biomarkers to select strategies and dual combination treatments. 

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