Pembrolizumab and other immune checkpoint inhibitors in locally advanced or metastatic Merkel Cell Carcinoma: safety and efficacy

Expert Rev Anticancer Ther. 2020 Dec;20(12):1093-1106. doi: 10.1080/14737140.2021.1835477. Epub 2020 Nov 4.

Abstract

Introduction: Merkel Cell Carcinoma (MCC) is a rare aggressive skin cancer, mostly affecting elderly patients. Until recently, patients with advanced disease were treated with cytotoxic chemotherapies despite rapid chemoresistance and high toxicity. As with other cancers, immune checkpoint inhibitors (CPI), including pembrolizumab, allow durable responses with a manageable safety profile in these patients.

Areas covered: This review describes the rationale for using PD-1/PD-L1 inhibitors in MCC, as well as efficacy and safety results from the three open-label trials investigating pembrolizumab or other PD-1/PD-L1 inhibitors in patients with advanced MCC. Real-life experience and predictive pre-treatment biomarkers are discussed to assess which patients are likely to be candidates for such strategies. Ongoing fields of research include the use of CPI in the adjuvant or neoadjuvant setting and combined strategies in refractory patients. Expert Opinion: CPI have become the standard of care for frontline treatment in patients with advanced MCC. Earlier introduction of CPI in the disease course, including neo-adjuvant and adjuvant settings, is likely to improve the outcomes further. Given the rarity of this cancer, we still need to harmonize efforts in order to conduct large-scale trials and efficiently identify best optimal care.

Keywords: Checkpoint inhibitor; Merkel Cell Carcinoma; immunotherapy; pembrolizumab; programmed cell death 1; skin cancer.

Publication types

  • Review

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • B7-H1 Antigen / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Merkel Cell / drug therapy*
  • Carcinoma, Merkel Cell / pathology
  • Drug Resistance, Neoplasm
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / pharmacology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab