Pembrolizumab for the treatment of colorectal cancer

Expert Opin Biol Ther. 2020 Mar;20(3):219-226. doi: 10.1080/14712598.2020.1718095. Epub 2020 Feb 3.

Abstract

Introduction: Colorectal cancer (CRC) is one of the most frequent and lethal cancers in the world, and therapies are still insufficient. Immune checkpoint inhibitors (ICI) in metastatic CRC (mCRC) have not revolutionized treatment to the extent that they have in melanoma or renal carcinoma. Their use is limited to a molecular niche of mCRC with microsatellite instability (MSI). This review summarizes clinical data published with pembrolizumab in mCRC and also tries to identify potential new strategies.Areas covered: This paper focuses on pembrolizumab in mCRC. We screened all trials on PubMed and ClinicalTrials.gov and describe the most significant ones in our opinion.Expert opinion: Pembrolizumab seems to be effective in tumors with MSI-high status. It defines a new horizon for therapeutic strategy called 'agnostic' medicine. For microsatellite stable (MSS) colorectal cancers, the future challenge will be to successfully redraw the immune microenvironment to make it immunogenic with new therapeutic combinations, including ICI.

Keywords: Colorectal cancer; immune checkpoint inhibitors; pembrolizumab; tumor mutational burden.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Cetuximab / therapeutic use
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / radiotherapy
  • Drug Therapy, Combination
  • Humans
  • Immunotherapy
  • Microsatellite Instability
  • Phenylurea Compounds / therapeutic use
  • Pyridines / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • pembrolizumab
  • Cetuximab