As reported in the Journal of Clinical Oncology by Yelena Y. Janjigian, MD, and colleagues, 3-year follow-up of the phase III CheckMate 649 trial has shown the continued benefit of the addition of nivolumab to chemotherapy in the first-line treatment of advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma.
The trial supported the April 2021 approval of nivolumab plus chemotherapy in this setting, regardless of PD-L1 expression status.
Yelena Y. Janjigian, MD
Study Details
In the trial, patients were randomly assigned to receive nivolumab plus chemotherapy (n = 789) or chemotherapy alone (n = 792). Chemotherapy consisted of modified FOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin). In the primary analysis, the nivolumab group had significantly better overall survival and progression-free survival on blinded independent central review among the 473 vs 482 patients with a PD-L1 combined positive score (CPS) ≥ 5, the primary endpoints. In the total population, the nivolumab group also showed superior overall survival and progression-free survival irrespective of PD-L1 expression status.
Key Findings
After a minimum follow-up of 36.2 months, the hazard ratio for overall survival in the nivolumab group vs the control group among patients with PD-L1 CPS ≥ 5 was 0.70 (95% confidence interval [CI] = 0.61–0.81), with 21% vs 10% of patients remaining alive at 36 months. The hazard ratio for progression-free survival was 0.70 (95% CI = 0.60–0.81), with 36-month rates of 13% vs 8%.
Among all patients, irrespective of PD-L1 expression status, the hazard ratio for overall survival for the nivolumab vs control group was 0.79 (95% CI = 0.71–0.88), with 17% vs 10% of patients remaining alive at 36 months. The hazard ratio for progression-free survival was 0.79 (95% CI = 0.71–0.89), with 36-month rates of 11% vs 7%.
The objective response rate was 60% in the nivolumab group vs 45% in the control group; median response durations were 9.6 months vs 7.0 months.
The investigators concluded, “Adding nivolumab to chemotherapy maintained [a] clinically meaningful long-term survival benefit vs chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.”
Dr. Janjigian, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and Ono Pharmaceutical Company. For full disclosures of the study authors, visit ascopubs.org.
