Pembrolizumab Improves Response in HER2-Positive Gastric Cancer

Standard treatment of advanced HER2-positive esophagogastric cancer combines trastuzumab with fluorinated pyrimidine/platinum-based chemotherapy. Investigators now report a planned interim analysis of response rates in the industry-sponsored, international, phase 3 KEYNOTE-811 trial in which patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma were randomized to treatment with either pembrolizumab (200 mg every 3 weeks) or placebo along with trastuzumab and investigator's choice of capecitabine/oxaliplatin or infusional 5-FU/cisplatin.

Of 433 patients randomized, 81% were male, 68% had gastric primary tumors, 81% were immunohistochemistry positive at 3+ for HER2, and 84% were PD-L1–positive at ≥1%. In this interim efficacy analysis of 264 patients, the pembrolizumab arm had a significantly higher response rate compared with placebo (74.4% vs. 51.9%; P=0.00006), deeper response (change from baseline, 65% vs. 49%), higher rate of complete response (11.3% vs. 3.1%), and higher rate of disease control (96.2% vs. 89.3%). Patients with a combined positive score (CPS) <1% had a smaller incremental increase in response with pembrolizumab than those with a CPS ≥1% (4.6% vs. 25.2%). Median response duration was similar with pembrolizumab and placebo (10.6 and 9.5 months). No new safety signals were observed.