Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer

Esophageal cancer (EC) is the seventh most common malignancy worldwide. Although systemic chemotherapy is the standard treatment for advanced EC, the available cytotoxic agents have limited efficacy. Pembrolizumab, a humanized monoclonal immunoglobulin G4 antibody that inhibits programmed cell death...

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Main Authors: Toshiharu Hirose, Shun Yamamoto, Ken Kato
Format: Article
Language:English
Published: SAGE Publishing 2023-01-01
Series:Therapeutic Advances in Gastroenterology
Online Access:https://doi.org/10.1177/17562848221148250
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author Toshiharu Hirose
Shun Yamamoto
Ken Kato
author_facet Toshiharu Hirose
Shun Yamamoto
Ken Kato
author_sort Toshiharu Hirose
collection DOAJ
description Esophageal cancer (EC) is the seventh most common malignancy worldwide. Although systemic chemotherapy is the standard treatment for advanced EC, the available cytotoxic agents have limited efficacy. Pembrolizumab, a humanized monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein 1, has recently been developed for the treatment of patients with advanced EC. In the KEYNOTE-181 trial, pembrolizumab achieved a clinical meaningful overall survival benefit over chemotherapy alone when used as second-line treatment in patients with esophageal squamous cell carcinoma (ESCC) who had a combined positive score ⩾10 for expression of programmed death ligand 1. Furthermore, KEYNOTE-590 showed that pembrolizumab + chemotherapy was more effective than chemotherapy alone as first-line chemotherapy for patients with advanced EC. Accordingly, immune checkpoint inhibitor (ICI) chemotherapy has become the standard first-line treatment for advanced EC. The use of ICIs in primary therapy has helped to improve the prognosis, especially for ESCC. Moreover, in CheckMate 577, patients who received postoperative nivolumab therapy had a reduced risk of recurrence, and the ability of preoperative ICI chemotherapy to reduce the incidence of recurrence is now under investigation. This review outlines the evidence for use of pembrolizumab as a first-line treatment for advanced unresectable or metastatic EC, summarizes the ongoing research on ICI combination chemotherapy, and discusses the associated issues.
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spelling doaj.art-e011f8ca8436413ba7237fcd154fd4cd2023-01-11T14:04:38ZengSAGE PublishingTherapeutic Advances in Gastroenterology1756-28482023-01-011610.1177/17562848221148250Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancerToshiharu HiroseShun YamamotoKen KatoEsophageal cancer (EC) is the seventh most common malignancy worldwide. Although systemic chemotherapy is the standard treatment for advanced EC, the available cytotoxic agents have limited efficacy. Pembrolizumab, a humanized monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein 1, has recently been developed for the treatment of patients with advanced EC. In the KEYNOTE-181 trial, pembrolizumab achieved a clinical meaningful overall survival benefit over chemotherapy alone when used as second-line treatment in patients with esophageal squamous cell carcinoma (ESCC) who had a combined positive score ⩾10 for expression of programmed death ligand 1. Furthermore, KEYNOTE-590 showed that pembrolizumab + chemotherapy was more effective than chemotherapy alone as first-line chemotherapy for patients with advanced EC. Accordingly, immune checkpoint inhibitor (ICI) chemotherapy has become the standard first-line treatment for advanced EC. The use of ICIs in primary therapy has helped to improve the prognosis, especially for ESCC. Moreover, in CheckMate 577, patients who received postoperative nivolumab therapy had a reduced risk of recurrence, and the ability of preoperative ICI chemotherapy to reduce the incidence of recurrence is now under investigation. This review outlines the evidence for use of pembrolizumab as a first-line treatment for advanced unresectable or metastatic EC, summarizes the ongoing research on ICI combination chemotherapy, and discusses the associated issues.https://doi.org/10.1177/17562848221148250
spellingShingle Toshiharu Hirose
Shun Yamamoto
Ken Kato
Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
Therapeutic Advances in Gastroenterology
title Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
title_full Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
title_fullStr Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
title_full_unstemmed Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
title_short Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
title_sort pembrolizumab for first line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer
url https://doi.org/10.1177/17562848221148250
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