Ipilimumab/Nivolumab Not Superior to Chemotherapy in Gastric Cancer

Regulatory approval was granted for first-line use of nivolumab combined with FOLFOX in metastatic gastroesophageal cancer based on results of the industry-sponsored, phase 3 CHECKMATE 649 trial. The trial demonstrated improvements in response, progression-free survival (PFS), and overall survival (OS) at 12-month follow up in the target population of patients with programmed cell death-ligand 1 (PDL-1) combined positive scores (CPS) >5% and in all patients treated (NEJM JW Oncol Hematol Aug 2021 and Lancet 2021; 398:27). There is ongoing debate about the utility of nivolumab in patients with low or negative expression of PDL-1.

Investigators now report updated results from CHECKMATE 649 at a minimum follow up of 24 months, including findings for a treatment arm receiving ipilimumab plus nivolumab compared to the arm receiving FOLFOX chemotherapy alone. Ipilimumab/nivolumab was not superior to FOLFOX in patients with CPS >5% (median OS, 11.2 and 11.6 months; median PFS, 2.8 vs. 6.3 months) or in all patients treated (median OS, 11.7 and 11.8 months; median PFS, 2.8 vs. 7.1 months). The ipilimumab/nivolumab group had a lower response rate than the FOLFOX chemotherapy group (27% vs. 47%). Although a survival benefit for nivolumab plus FOLFOX over FOLFOX alone was maintained at 24 months in patients with CPS >5% (proportion of patients alive, 31% vs. 19%), there was no clear OS benefit in the subgroups of patients with CPS <10% (hazard ratio, 0.91), <5% (HR, 0.94), or <1% (HR, 0.95).