Cardiac toxicity of HER-2 targeting antibody-drug conjugates: overview and clinical implications

Future Oncol. 2024;20(38):3151-3167. doi: 10.1080/14796694.2024.2407756. Epub 2024 Oct 7.

Abstract

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

Keywords: HER-2; T-DM1; T-DXd; antibody–drug conjugates; cardio-oncology; cardiotoxicity.

Plain language summary

[Box: see text].

Publication types

  • Review

MeSH terms

  • Ado-Trastuzumab Emtansine / administration & dosage
  • Ado-Trastuzumab Emtansine / adverse effects
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Cardiotoxicity* / diagnosis
  • Cardiotoxicity* / etiology
  • Cardiotoxicity* / prevention & control
  • Humans
  • Immunoconjugates* / administration & dosage
  • Immunoconjugates* / adverse effects
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Receptor, ErbB-2* / antagonists & inhibitors
  • Receptor, ErbB-2* / metabolism
  • Trastuzumab / administration & dosage
  • Trastuzumab / adverse effects

Substances

  • Ado-Trastuzumab Emtansine
  • Antineoplastic Agents, Immunological
  • ERBB2 protein, human
  • Immunoconjugates
  • Receptor, ErbB-2
  • Trastuzumab
  • trastuzumab deruxtecan