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 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.