Dr Janjigian on Safety Considerations With Nivolumab Plus Chemotherapy in Gastric/GEJ/Esophageal Cancer

"The safety [profile] has been steadily the same across every time point [when] we have updated the data. I don’t take it for granted being able to keep updating and seeing the same reliable [safety] results.”

Yelena Y. Janjigian, MD, chief, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, discussed the safety profile of nivolumab (Opdivo) in combination with chemotherapy for the first-line treatment of patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma.

During the 2025 Gastrointestinal Cancers Symposium, Janjigian presented findings from the 5-year follow-up analysis of the phase 3 CheckMate 649 trial (NCT02872116). Patients with untreated, advanced or metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma who received nivolumab plus chemotherapy (n = 789) achieved a median overall survival of 13.7 months (95% CI, 12.4-14.5) vs 11.6 months (95% CI, 10.9-12.5) among patients who received chemotherapy alone (n = 792; HR, 0.79; 95% CI, 0.71-0.88).

Janjigian noted that the safety profile of the combination has been consistent across data updates. Treatment with immune checkpoint inhibitors can cause immune-related adverse effects (AEs) which mostly occur within the first 3 months of treatment, she added. These AEs can be well managed with dose interruption or topical steroids for skin-related toxicities, she said.

In the safety population of CheckMate 649, patients who received the combination (n = 782) experienced any-grade treatment-related AEs (TRAEs) at a rate of 95%; any-grade serious TRAEs and TRAEs leading to treatment discontinuation occurred at rates of 23% and 42%, respectively. The most common grade 3 or 4 TRAEs in the combination arm included neutropenia (16%), decreased neutrophil count (11%), anemia (6%), and increased lipase levels (6%).

Autoimmune hepatitis and acute interstitial nephritis can lead to therapy discontinuation with nivolumab plus chemotherapy, but instances of these AEs are rare, Janjigian said. Overall, the AEs observed with the combination are mostly due to systemic chemotherapy and adjusting the chemotherapy regimen based on patient characteristics such as age will allow more patients to receive the combination, she continued. In general, once patients have completed the entire course of upfront therapy, the continuation of fluorouracil or capecitabine plus nivolumab as maintenance therapy is very well tolerated, Janjigian said in conclusion.