Multinational phase 3 trial of perioperative pembrolizumab plus chemotherapy for locally advanced gastric or gastro-esophageal cancer

The benefit of combination of neoadjuvant and adjuvant chemotherapy and immune checkpoint inhibition in patients with locally advanced, resectable gastric or gastro-esophageal adenocarcinoma is unknown. The phase 3 KEYNOTE-585 trial (142 centers in 24 countries) evaluated addition of pembrolizumab or placebo to neoadjuvant chemotherapy, followed by surgery and adjuvant pembrolizumab or placebo plus chemotherapy, and pembrolizumab or placebo maintenance. Addition of pembrolizumab to neoadjuvant chemotherapy was associated with improved pathologic complete response rate (12.9% versus 2.0%; p<0.00001). The event-free survival (median 44.4 months versus 25.3 months; HR 0.81; p=0.0198) and overall survival (median 60.7 months versus 58.0 months) were not statistically significant improved with pembrolizumab over placebo. Grade 3 or worse adverse events of any cause were reported for 78% of patients with pembrolizumab and 74% of patients with placebo.