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.
K Kato, J Ajani, Y Doki et al.
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In 30 seconds
This open-label, phase III randomized trial compared first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, and chemotherapy in patients with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma. At a minimum follow-up of 5 years, both nivolumab regimens were associated with longer overall survival than chemotherapy among patients with tumor-cell PD-L1 expression ≥1% (HR 0.62 for each comparison). Overall-survival benefit was also observed in all randomly assigned patients. Progression-free survival benefit in the PD-L1 ≥1% group was observed with nivolumab plus chemotherapy, but not with nivolumab plus ipilimumab.
Key findings
- For tumor-cell PD-L1 ≥1%, overall survival favored nivolumab plus chemotherapy versus chemotherapy (HR 0.62, 95% CI 0.48-0.79) and nivolumab plus ipilimumab versus chemotherapy (HR 0.62, 95% CI 0.48-0.80).
- In all randomly assigned patients, overall survival favored both nivolumab regimens versus chemotherapy (HR 0.77, 95% CI 0.65-0.92 for each comparison).
- In the PD-L1 ≥1% population, progression-free survival favored nivolumab plus chemotherapy (HR 0.67, 95% CI 0.51-0.88), but not nivolumab plus ipilimumab (HR 1.03, 95% CI 0.78-1.35).
- Grade 3-4 treatment-related adverse events occurred in 49% with nivolumab plus chemotherapy, 33% with nivolumab plus ipilimumab, and 37% with chemotherapy.
Why it matters
The 5-year follow-up indicates that overall-survival benefit with either nivolumab-containing regimen versus chemotherapy persisted in this advanced cancer population. The differing progression-free survival results and adverse-event rates provide useful context when interpreting the regimens’ benefits and harms. The findings extend the evidence beyond earlier follow-up, while remaining specific to the trial population and comparisons.
What to keep in mind
The trial was open-label, and the abstract reports outcomes at a minimum follow-up rather than a uniform follow-up duration.