Dr Janjigian on 5-Year Data With Nivolumab Plus Chemotherapy in Gastric/GEJ/Esophageal Cancer

“The purpose of these updated analyses is really to see how the curves evolve over time. We know that the survival was improved at the median and at the hazard ratio time point of one year, two years, and so forth. But the question remains, over time, will these curves converge?The survival curves do not converge, crossover, or overlap, and this sustained separation is a very powerful message to our patients.”

Yelena Y. Janjigian, MD, chief, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the long-term efficacy and clinical significance of the 5-year follow-up results from the phase 3 CheckMate 649 trial (NCT02872116), which evaluated nivolumab (Opdivo) plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma.

The updated analysis, presented at the 2025 Gastrointestinal Cancers Symposium, represents the longest reported follow-up for a PD-1 inhibitor–based regimen in this patient population. Previous results demonstrated a survival benefit at 1 year, 2 years, and beyond, but long-term follow-up was needed to determine whether the survival curves would converge over time, Janjigian explains.

The 5-year data confirm a sustained survival benefit with nivolumab plus chemotherapy across all randomized patients and across PD-L1 combined positive score (CPS) subgroups (CPS ≥1, CPS ≥5, and CPS ≥10), she continues. The objective response rate (ORR) was also higher, and duration of response (DOR) was longer in patients receiving nivolumab-based therapy. Notably, the survival curves remained separated over time, with 10% to 20% of patients with stage IV disease still alive at 5 years despite the aggressive nature of their disease, she reports.

These findings reinforce nivolumab plus chemotherapy as the standard first-line therapy for patients with advanced gastric, GEJ, and esophageal cancer, Janjigian emphasizes. Although median overall survival (OS) improvements may appear modest, the presence of long-term survivors highlights the effect of this treatment approach, she adds. The benefit was particularly pronounced in patients with higher PD-L1 expression, further supporting PD-L1 testing to guide treatment decisions.

No new safety concerns were observed during extended follow-up, further solidifying nivolumab’s acceptable long-term safety profile, she notes. These data underscore the durable benefit of checkpoint inhibition in gastroesophageal cancers and provide important long-term insights to guide patient management, Janjigian concludes.