First-line nivolumab plus chemotherapy or ipilimumab versus chemotherapy for advanced ESCC: five-year follow-up results from CheckMate 648

The multinational phase 3 CheckMate 648 trial found an overall survival (OS) benefit with nivolumab plus chemotherapy and with nivolumab plus ipilimumab compared with chemotherapy for patients with previously untreated advanced esophageal squamous cell carcinoma (aESCC). Five-year results from CheckMate 648 have now been published. A total of 970 patients were randomized 1:1:1 to nivolumab plus chemotherapy (n=321), nivolumab plus ipilimumab (n=325), or chemotherapy (n=324. At 5-year minimum follow-up, in patients with tumor cell PD-L1 ≥ 1%, OS improvement continued to be observed with nivolumab plus chemotherapy versus chemotherapy (HR 0.62; 95% CI 0.48-0.79) and with nivolumab plus ipilimumab versus chemotherapy (0.62; 0.48-0.80). OS benefit was also observed in all randomized patients for both nivolumab plus chemotherapy and nivolumab plus ipilimumab versus chemotherapy (HR 0.77; 95% CI 0.65-0.92). In the tumor cell PD-L1 ≥ 1% population , progression-free survival (PFS) benefit was observed with nivolumab plus chemotherapy versus chemotherapy (HR 0.67; 95% CI 0.51-0.88) but not with nivolumab plus ipilimumab versus chemotherapy (1.03; 0.78-1.35). Among all treated patients, grade 3-4 treatment-related adverse events were observed in 49% of the patients in the nivolumab plus chemotherapy group, 33% of the patients in the nivolumab plus ipilimumab group, and 37% of the patients in the chemotherapy group. The authors conclude that nivolumab-containing regimens continued to demonstrate clinically meaningful OS benefit versus chemotherapy at 5-year follow-up, with no new safety signals.