Nivolumab (PD-1) + chemo or nivolumab + ipilimumab (CTLA-4) sustains OS benefit at 5 years in 1L advanced ESCC

Nivolumab, a PD-1 checkpoint inhibitor, combined with platinum/fluoropyrimidine chemotherapy—or paired with ipilimumab (CTLA-4)—was evaluated versus chemotherapy alone in the open-label Phase 3 CheckMate 648 trial (NCT03143153) for previously untreated unresectable/recurrent/metastatic ESCC (n=970). At ≥5-year minimum follow-up, OS benefit persisted in tumor-cell PD-L1 ≥1% patients for nivolumab+chemo vs chemo (HR 0.62, 95% CI 0.48–0.79) and nivolumab+ipilimumab vs chemo (HR 0.62, 95% CI 0.48–0.80); in all randomized patients, OS HR was 0.77 (95% CI 0.65–0.92) for both regimens vs chemo—building on the original CheckMate 648 benchmark where chemo mOS was ~10.7 months overall and ~9.1 months in PD-L1 ≥1% (vs nivolumab+chemo ~13.2 and ~15.4 months, respectively). PFS separated only for nivolumab+chemo in PD-L1 ≥1% (HR 0.67, 95% CI 0.51–0.88), while nivolumab+ipilimumab did not improve PFS (HR 1.03, 95% CI 0.78–1.35); grade 3/4 TRAEs were 49% (nivo+chemo), 33% (nivo+ipi), and 37% (chemo), aligning with the practical trade-off vs PD-1+chemo SOC alternatives like KEYNOTE-590 (pembrolizumab+chemo improved OS in ESCC CPS ≥10: mOS ~13.9 vs 8.8 months).