Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics

Expert Opin Biol Ther. 2021 Jul;21(7):945-962. doi: 10.1080/14712598.2021.1936494. Epub 2021 Jun 15.

Abstract

Introduction: Advanced breast cancer (aBC) remains incurable and the quest for more effective systemic anticancer agents continues. Promising results have led to the FDA approval of three antibody-drug conjugates (ADCs) and two immune checkpoint inhibitors (ICIs) to date for patients with aBC.

Areas covered: With the anticipated emergence of newer ADCs and ICIs for patients with several subtypes of breast cancer, and given their potential synergy, their use in combination is of clinical interest. In this article, we review the use of ADCs and ICIs in patients with breast cancer, assess the scientific rationale for their combination, and provide an overview of ongoing trials and some early efficacy and safety results of such dual therapy.

Expert opinion: Improvement in the medicinal chemistry of next-generation ADCs, their rational combination with ICIs and other agents, and the development of multiparametric immune biomarkers could help to significantly improve the outlook for patients with refractory aBC.

Keywords: Breast cancer; antibody–drug conjugate; atezolizumab; bystander effect; dual therapy; immune checkpoint inhibitor; pembrolizumab; sacituzumab govitecan; trastuzumab deruxtecan; trastuzumab emtansine.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunoconjugates* / therapeutic use
  • Immunotherapy

Substances

  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors
  • Immunoconjugates