The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) amplification or overexpression occurs in approximately 20% of advanced gastric or gastro-oesophageal junction adenocarcinomas(1-3). More than a decade ago, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy became the standard first-line treatment for patients with these types of tumours(4). Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer(5), there are preclinical(6-19) and clinical(20,21) rationales for adding pembrolizumab in HER2-positive disease. Here we describe results of the protocol-specified first interim analysis of the randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study of pembrolizumab plustrastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma 22 (https://clinicaltrials.gov, NCT03615326). We show that adding pembrolizumab to trastuzumab and chemotherapy markedly reduces tumour size, induces complete responses in some participants, and significantly improves objective response rate.

Automated summary

The study results demonstrate that adding pembrolizumab to trastuzumab and chemotherapy significantly reduces tumor size, induces complete responses in some patients, and improves objective response rate in HER2-positive gastric or gastro-oesophageal junction adenocarcinoma.