Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): 45-month (mo) follow-up from CheckMate 648.

4034 Background: NIVO + chemo and NIVO + IPI are approved for the treatment of advanced ESCC in the US, EU, Japan, and many other countries based on the results from CheckMate 648 (NCT03143153). Here, we report 45-mo follow-up results. Methods: Adults with previously untreated, unresectable advanced, recurrent, or metastatic ESCC were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W) or chemo. The primary endpoints were overall survival (OS) and progression-free survival (PFS) per blinded independent central review (BICR) in patients (pts) with tumor cell programmed death ligand 1 (PD-L1) ≥ 1%. Results: In total, 970 pts were randomized to NIVO + chemo, NIVO + IPI, or chemo. With 45-mo minimum follow-up, NIVO + chemo and NIVO + IPI demonstrated continued OS benefit and higher 45-mo OS rates vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Duration of response (DOR) was longer (Table) and the proportion of responders with DOR ≥ 45 mo was greater with NIVO + chemo and NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% (7% and 23% vs 0%, respectively) and all randomized pts (14% and 18% vs 6%). Any-grade treatment-related adverse events (TRAEs) occurred in 96% of pts with NIVO + chemo, 80% with NIVO + IPI, and 90% with chemo; grade 3/4 TRAEs occurred in 49%, 33%, and 37% of pts, respectively. No additional TRAEs leading to discontinuation and no new treatment-related deaths were reported with longer follow-up. Conclusions: After 45 mo of follow-up, NIVO + chemo and NIVO + IPI continued to demonstrate clinically meaningful survival benefit and more durable responses vs chemo, with no new safety signals. These results further support NIVO + chemo and NIVO + IPI as 1L treatment options for advanced ESCC. Clinical trial information: NCT03143153 . Table: see text