Immune checkpoint inhibition for the treatment of mesothelioma

Expert Opin Biol Ther. 2019 Jul;19(7):697-706. doi: 10.1080/14712598.2019.1606209. Epub 2019 May 2.

Abstract

Introduction: Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.

Areas covered: This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.

Expert opinion: Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.

Keywords: Antineoplastic therapy; biomarkers; checkpoint blockade; immunotherapy; mesothelioma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / metabolism
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Drug Therapy, Combination
  • Humans
  • Immunotherapy
  • Mesothelioma / drug therapy*
  • Mesothelioma / pathology
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human