Sintilimab Added to Chemotherapy for Advanced Esophagogastric Adenocarcinoma

Immune checkpoint inhibitors targeting PD-1 have been shown to improve response, progression-free survival, and overall survival when combined with first-line chemotherapy in patients with metastatic esophagogastric cancer. Investigators in China now report results of ORIENT-16, an industry-sponsored, randomized, double-blind, placebo-controlled trial evaluating the addition of sintilimab to first-line chemotherapy in patients with advanced esophagogastric adenocarcinoma. Patients received capecitabine and oxaliplatin every 3 weeks combined with either placebo or sintilimab (3 mg/kg in patients <60 kg or 200 mg in patients >60 kg) for up to six cycles.

Of the 650 patients enrolled, 81% had gastric primary tumors, 39% had liver metastases, and 61% had PD-L1 combined positive scores (CPS) >5%. The primary endpoint of overall survival was improved with sintilimab compared with placebo in patients with CPS >5% (median, 18.4 vs. 12.9 months; hazard ratio, 0.66; P=0.002) and in all randomized patients (median,15.2 vs. 12.3 months; HR, 0.77; P=0.009). No survival benefit with sintilimab was seen in patients with CPS <5% (HR, 0.90). Among patients with CPS >5% PFS was improved with sintilimab over placebo (7.7 vs. 5.8 months; HR, 0.63; P< 0.001) as was response rate (63.6% vs. 49.4%, respectively; P=0.008). No new safety signals were observed.