Nivolumab plus chemotherapy or ipilimumab versus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma: 5-year follow-up results from CheckMate 648.

In previously untreated advanced esophageal squamous cell carcinoma with tumor cell PD-L1 ≥1%, nivolumab plus chemotherapy or nivolumab plus ipilimumab improved overall survival at 5 years (HR 0.62 for both).

• Why it matters: Long-term outcomes and safety beyond initial follow-up are needed to confirm whether nivolumab-based first-line regimens sustain survival gains versus chemotherapy in advanced ESCC.
• What they did: In the open-label phase III CheckMate 648 trial (NCT03143153), 970 patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy, with OS assessed by blinded independent central review.
• The result: At minimum 5-year follow-up, OS benefit persisted in PD-L1 ≥1% (HR 0.62, 95% CI 0.48–0.79 and 0.48–0.80) and in all randomized patients (HR 0.77, 95% CI 0.65–0.92), with no new safety signals.

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