(Esophageal Cancer) Is Opdivo + Yervoy Effective?

• February 18, 2022
• Reading time: 2 minutes

On February 3, 2022, Yuichiro Doki and colleagues from the Osaka University Graduate School of Medicine published results in The New England Journal of Medicine from the CheckMate 648 Phase III clinical trial evaluating first-line nivolumab (Opdivo, anti-PD-1) plus ipilimumab (Yervoy, anti-CTLA-4) or nivolumab plus chemotherapy in previously untreated, unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma patients.

The CheckMate 648 trial randomized previously untreated, unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma patients (N=970) in a 1:1:1 ratio to: nivolumab + ipilimumab arm (nivolumab 3 mg/kg every 2 weeks, ipilimumab 1 mg/kg every 6 weeks), nivolumab + chemotherapy arm (nivolumab 240 mg every 2 weeks), or chemotherapy arm. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoint was objective response rate (ORR).

Results at median follow-up of 13 months:

Overall Survival (Primary Endpoint): In PD-L1-positive patients, median OS was 15.4 months in the nivolumab + chemotherapy arm versus 9.1 months in the chemotherapy arm — a 46% significant improvement in mortality risk. In all patients, median OS was 13.2 months versus 10.7 months, representing a 26% reduction in mortality risk.

For the nivolumab + ipilimumab arm in PD-L1-positive patients, median OS was 13.7 months — a 36% improvement in mortality risk versus chemotherapy. In all patients, median OS was 12.7 months — a 22% reduction in mortality risk.

Progression-Free Survival (Primary Endpoint): In PD-L1-positive patients, the nivolumab + chemotherapy arm showed a significant 35% improvement in progression risk versus chemotherapy. The nivolumab + ipilimumab arm did not show a significant improvement in PFS versus chemotherapy.

Safety: Grade 3–4 adverse events occurred in 32% of the nivolumab + ipilimumab arm, 47% of the nivolumab + chemotherapy arm, and 36% of the chemotherapy arm.

Based on the CheckMate 648 trial results, Doki and colleagues concluded that both the nivolumab + chemotherapy and nivolumab + ipilimumab arms demonstrated significant OS improvements versus chemotherapy in previously untreated, unresectable advanced or metastatic esophageal squamous cell carcinoma patients, with safety profiles consistent with existing clinical data.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2111380?query=featured_home

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