Pembrolizumab for recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus: a drug safety evaluation

ABSTRACT

Introduction

The prognosis of advanced esophageal squamous cell carcinoma (ESCC) remains poor and few effective drugs are available. Cisplatin plus 5-FU (CF) has been the standard first-line treatment for advanced ESCC. However, in the KEYNOTE-181 trial, the clinical outcomes were better in patients with programmed death ligand 1 (PD-L1)-positive advanced ESCC who received pembrolizumab, an immune checkpoint inhibitor (ICI), than in those who received cytotoxic agents as second-line treatment. Moreover, the KEYNOTE-590 trial demonstrated the superiority of pembrolizumab plus CF over CF alone in terms of overall survival. Based on the results of KEYNOTE-590, pembrolizumab plus CF has become one of the standard treatments for advanced ESCC. However, the safety profile of ICI-containing therapy is different from that of conventional cytotoxic agents.

Areas covered

Safety of pembrolizumab-containing therapies in patients with advanced ESCC.

Expert opinion

Pembrolizumab-containing therapies are tolerable as first- and second-line treatments in patients with advanced ESCC. Although infrequent, immune-related adverse events may occur in patients on pembrolizumab-containing therapies. These events are potentially fatal and require treatment with steroids or immunosuppressive drugs. Regular physical and laboratory examinations, including measurement of hormone levels, are needed during and after pembrolizumab-containing therapies in clinical practice.

KEYWORDS:

• Esophageal cancer
• esophageal squamous cell carcinoma
• first-line treatment
• immune-related adverse event
• pembrolizumab

Article highlights

• The prognosis of advanced esophageal cancer has been poor, with few effective therapeutic agents.

• Pembrolizumab is a novel human monoclonal antibody that targets programmed cell death protein 1

• Pembrolizumab monotherapy was approved by the US Food and Drug Administration on 30 July 2019 as chemotherapy for patients with PD-L1-positive esophageal squamous cell carcinoma who experienced disease progression after one or more lines of systemic chemotherapy.

• Pembrolizumab was approved by the US Food and Drug Administration on 22 March 2021 for use in combination with platinum and fluoropyrimidine-based chemotherapy in patients with metastatic or locally advanced esophageal or gastroesophageal cancer not amenable to surgical resection or definitive chemoradiation.

• Immune checkpoint inhibitors are associated with fewer treatment-related adverse events than conventional cytotoxic agents. However, in some cases, serious immune-related adverse events such as pneumonia, fulminant type 1 diabetes. and myocarditis, have been reported. When immune-related adverse events occur, immune checkpoint inhibitors should be discontinued; addition of high-dose steroids, immunosuppressive drugs, and hormone replacement therapy might be necessary.

Declaration of interest

K Kato has declared research funds from ONO, MSD, Merck Bio, Bristol Myers Squibb, Taiho, Chugai, Oncolys Biopharma and Shionogi.

S Yamamoto has declared honoraria from ONO and MSD, Bristol Myers Squibb, Taih.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.