Emerging drugs for the treatment of triple-negative breast cancer: a focus on phase II immunotherapy trials

Expert Opin Emerg Drugs. 2021 Jun;26(2):131-147. doi: 10.1080/14728214.2021.1916468. Epub 2021 Apr 19.

Abstract

Introduction: Triple-negative breast cancer accounts for 10-20% of invasive breast cancers and is characterized by an aggressive phenotype and poor outcomes in the early and advanced settings compared to other breast cancer subtypes. Chemotherapy continues to be the mainstay of treatment, but recent advances have demonstrated the benefit of adding immune checkpoint inhibitors (ICIs) to chemotherapy regimens for patients with both early and advanced TNBC, particularly if PD-L1-positive. Despite these results, further improvements are needed.Areas covered: This review covers immunotherapy drugs which have recently completed, involved in ongoing or due to start phase II trials. This includes approaches to augment the response to existing ICIs, next-generation ICIs, combination treatments with targeted agents and drugs that target the tumor microenvironment. Potential development issues are also discussed.Expert opinion: The field of immunotherapy is developing rapidly and holds great promise for patients with TNBC. Promising avenues of research currently in phase II trials include targeting multiple immune checkpoints simultaneously and the addition of phosphatidylinositol 3-kinase (PI3K)/AKT inhibitors to ICI/chemotherapy regimens. A better understanding of the immunosuppressive role played by the tumor microenvironment has also been important. However, challenges remain, particularly regarding the need for more effective predictive biomarkers.

Keywords: Advanced TNBC; early TNBC; immune checkpoint; immunotherapy; targeted therapies; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Clinical Trials, Phase II as Topic
  • Drug Design
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunotherapy / methods*
  • Molecular Targeted Therapy
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / immunology
  • Tumor Microenvironment / immunology

Substances

  • Immune Checkpoint Inhibitors