The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer
Yelena Y Janjigian, Akihito Kawazoe, Patricio Yañez, Ning Li, Sara Lonardi, Oleksii Kolesnik, Olga Barajas, Yuxian Bai, Lin Shen, Yong Tang, Lucjan S Wyrwicz, Jianming Xu, Kohei Shitara, Shukui Qin, Eric Van Cutsem, Josep Tabernero, Lie Li, Sukrut Shah, Pooja Bhagia, Hyun Cheol Chung, Yelena Y Janjigian, Akihito Kawazoe, Patricio Yañez, Ning Li, Sara Lonardi, Oleksii Kolesnik, Olga Barajas, Yuxian Bai, Lin Shen, Yong Tang, Lucjan S Wyrwicz, Jianming Xu, Kohei Shitara, Shukui Qin, Eric Van Cutsem, Josep Tabernero, Lie Li, Sukrut Shah, Pooja Bhagia, Hyun Cheol Chung
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://ichgcp.net/clinical-trials-registry/NCT03615326" title="See in 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.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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Source: PubMed