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The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer
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The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer
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Journal Article
The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer
2021
Overview
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 plus trastuzumab 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.
Interim analysis of a phase III clinical trial of HER2-positive gastric adenocarinoma shows pembrolizumab plus trastuzumab and chemotherapy improves response rates compared with trastuzumab and chemotherapy alone.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adenocarcinoma - drug therapy
/ Antibodies, Monoclonal, Humanized - pharmacology
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Antineoplastic Combined Chemotherapy Protocols - pharmacology
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Cancer
/ Esophagogastric Junction - drug effects
/ Esophagogastric Junction - pathology
/ Humanities and Social Sciences
/ Humans
/ Ligands
/ Programmed Cell Death 1 Receptor - antagonists & inhibitors
/ Receptor, ErbB-2 - antagonists & inhibitors
/ Receptor, ErbB-2 - metabolism
/ Science
/ Stomach Neoplasms - drug therapy
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - pathology
/ Testing
/ Trastuzumab - therapeutic use
/ Tumors
