Multicenter phase 3 trial of sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer

Patients with unresectable gastric and gastroesophageal junction (G/GEJ) cancers have limited therapeutic options. The phase 3 ORIENT-16 trial, at 62 centers in China, evaluated addition of sintilimab (anti-PD-1) to first-line chemotherapy among 650 patients with unresectable locally advanced or metastatic G/GEJ adenocarcinoma. Patients were randomized 1:1 to either sintilimab or placebo, both combined with XELOX chemotherapy. Among all randomized patients, sintilimab improved overall survival compared with placebo (median 15.2 versus 12.3 months; HR 0.77; p=0.009). Among patients with a PD-L1 combined positive score of 5 or more, the median overall survival was 18.4 months in the sintilimab group versus 12.9 months in the placebo group (HR 0.66; p=0.002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (24.7% of patients with sintilimab versus 21.3% with placebo), decreased neutrophil count (20.1% versus 18.8%), and anemia (12.5% versus 8.8%). The authors conclude that among patients with previously untreated unresectable locally advanced or metastatic G/GEJ adenocarcinoma, addition of sintilimab to chemotherapy significantly improved overall survival (visual abstract).