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01-12-2021 | Esophageal Cancer | Review

The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials

Authors: Anwaar Saeed, Robin Park, Weijing Sun

Published in: Journal of Hematology & Oncology | Issue 1/2021

Abstract

Several targeted therapies have shown efficacy in patients with advanced gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJC), including anti-angiogenic agents and immune checkpoint inhibitors. Ramucirumab, an anti-VEGFR2 antibody, has shown efficacy in GC, but the benefits are limited, in part due to MET-mediated resistance. Other VEGF targeted agents like VEGF tyrosine kinase inhibitors (TKIs) with broad multi-kinase inhibitory spectrum like regorafenib and cabozantinib have also shown modest single agent activity in early phase trials. For immune checkpoint inhibitors, pembrolizumab (anti-PD-1) monotherapy confers survival advantage as 3rd line therapy for the PD-L1 expressing GC and GEJC population and has been approved for use in this setting. Extensive tumor microenvironment immune modulatory effects from antiangiogenic agents have been demonstrated from preclinical data which support the clinical study rationale of dual blockade of VEGF and immune checkpoint. In addition, FDA has approved combinations of anti-VEGF/VEGFR with anti-PD-1/PD-L1 agents in hepatocellular carcinoma and renal cell carcinoma. Promising clinical activity has been demonstrated in patients with refractory GC/GEJC when treated with dual blockade combination with antiangiogenic agents and immune checkpoint inhibitors like PD-1/PD-L1 inhibitors in several phase I/II trials. This review highlights the trials investigating these novel combinations as well as their preclinical rationale.

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Title: The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials
Authors: Anwaar Saeed
Robin Park
Weijing Sun
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Esophageal Cancer
Tyrosine Kinase Inhibitors
Gastric Cancer
Esophageal Cancer
Gastric Cancer
Tyrosine Kinase Inhibitors
Cabozantinib
Regorafenib
Ramucirumab
Checkpoint Inhibitors
Published in: Journal of Hematology & Oncology / Issue 1/2021
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-021-01034-0

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