Author:

Keywords:

Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, NIVOLUMAB PLUS CHEMOTHERAPY, GASTROESOPHAGEAL JUNCTION, RESPONSE CRITERIA, OPEN-LABEL, TRASTUZUMAB, ESOPHAGEAL, THERAPY, Adenocarcinoma, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Esophagogastric Junction, Humans, Programmed Cell Death 1 Receptor, Receptor, ErbB-2, Stomach Neoplasms, Trastuzumab, Receptor, erbB-2, General Science & Technology

Abstract:

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 adenocarcinomas1-3. 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 tumours4. Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer5, there are preclinical6-19 and clinical20,21 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 plus trastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma22 ( 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.