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

Expert Opin Drug Saf. 2024 Jun;23(6):667-675. doi: 10.1080/14740338.2024.2348554. Epub 2024 May 1.

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.

Publication types

  • Review
  • Comparative Study

MeSH terms

  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local* / drug therapy
  • Prognosis
  • Survival Rate

Substances

  • pembrolizumab
  • Antibodies, Monoclonal, Humanized
  • Immune Checkpoint Inhibitors
  • Antineoplastic Agents, Immunological
  • Fluorouracil