Pembrolizumab plus Chemotherapy for Patients with Advanced Gastric Cancer?

Studies of the anti–PD-1 immune checkpoint inhibitor pembrolizumab in patients with gastric cancer have had mixed results. Investigators now report findings from KEYNOTE-859, an industry-sponsored, placebo-controlled, double-blind, randomized phase 3 trial. The 1579 participants with HER2-negative, metastatic gastric or gastroesophageal junction (GEJ) cancer received pembrolizumab or placebo plus first-line chemotherapy (either infusional 5-FU combined with cisplatin or capecitabine combined with oxaliplatin) on a 3-week schedule.

Of the participants, 78% had a combined positive score (CPS) for PD-L1 of ≥1%, and 35% had CPS scores ≥10%. Most patients (79%) had gastric primaries, 78% had not undergone prior surgery, and 39% had hepatic metastases. Microsatellite instability–high-frequency tumors occurred in 5% of patients. At a median follow-up of 31 months, the primary endpoint of median overall survival (OS) in all patients was 12.9 months with pembrolizumab versus 11.5 months with placebo (hazard ratio, 0.78; P< 0.0001). Median OS with pembrolizumab was significantly better than with placebo in patients with CPS ≥1% (13.0 vs. 11.4 months; HR, 0.74) and in patients with CPS ≥10% (15.7 vs. 11.8 months; HR, 0.65). Patients with CPS ≤1% showed no OS benefit. Pembrolizumab was also associated with greater progression-free survival for all patients, those with CPS ≥1%, and those with CPS ≥10. In all participants, objective response was significantly greater with pembrolizumab than with placebo (51% vs. 42%). No new safety signals were observed.