Multinational phase 3 trial of pembrolizumab plus chemotherapy for HER2-negative advanced gastric/gastro-esophageal junction cancer

The multinational phase 3 KEYNOTE-859 trial (at 207 centers across 33 countries) evaluated first-line pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative locally advanced or metastatic gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. The primary end point was overall survival. Median follow-up at data cutoff was 31.0 months. In the ITT population, median overall survival was 12.9 months with pembrolizumab plus chemotherapy versus 11.5 months with placebo plus chemotherapy (HR 0.78; p<0.001). In the population with PD-L1 CPS of 1 or higher, median OS was 13.0 months versus 11.4 months (HR 0.74; p<0.0001). In the population with PD-L1 CPS of 10 or higher, median OS was 15.7 months versus 11.8 months (HR 0.65; p<0.0001). Serious treatment-related adverse events occurred in 23% of patients with pembrolizumab plus chemotherapy and 19% of patients with placebo plus chemotherapy, and treatment-related deaths in 1% and 2%, respectively. The authors conclude that the combination of pembrolizumab and chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative G/GEJ adenocarcinoma.