Cardiovascular Safety Assessment in Cancer Drug Development

J Am Heart Assoc. 2021 Dec 21;10(24):e024033. doi: 10.1161/JAHA.121.024033. Epub 2021 Dec 16.

Abstract

The development of cardiovascular toxicity attributable to anticancer drugs is a pivotal event that is associated with cardiovascular morbidity as well as with worse cancer-specific and overall outcomes. Although broad consensus exists regarding the importance of cardiovascular safety assessment in cancer drug development, real-world data suggest that cardiovascular events are significantly underestimated in oncology trials. This drug safety discrepancy has profound implications on drug development decisions, risk-benefit evaluation, formulation of surveillance and prevention protocols, and survivorship. In this article, we review the contemporary cardiovascular safety evaluation of new pharmaceuticals in hematology and oncology, spanning from in vitro pharmacodynamic testing to randomized clinical trials. We argue that cardiovascular safety assessment of anticancer drugs should be reformed and propose practical strategies, including development and validation of preclinical assays, expansion of oncology trial eligibility, incorporation of cardiovascular end points in early-phase studies, and design of longitudinal multi-institutional cardiotoxicity registries.

Keywords: antineoplastic agents; cardiotoxicity; cardiovascular safety; consensus; randomized controlled trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Cardiotoxicity* / epidemiology
  • Drug Development
  • Humans
  • Neoplasms / drug therapy

Substances

  • Antineoplastic Agents