Risk Stratification, Screening and Treatment of BRAF/MEK Inhibitors-Associated Cardiotoxicity

Curr Oncol Rep. 2024 Nov;26(11):1431-1441. doi: 10.1007/s11912-024-01599-2. Epub 2024 Sep 24.

Abstract

Purpose of review: In this review article we describe the cardiovascular adverse events associated with BRAF and MEK inhibitors as well as their pathophysiologic mechanisms and provide up to date guidance for risk stratified surveillance of patients on treatment and the optimal management of emergent cardiotoxicities.

Recent findings: Combination BRAF/MEK inhibition has become an established standard treatment option for patients with a wide variety of BRAF mutant haematological and solid organ cancers, its use is most commonly associated with stage three and metastatic melanoma. The introduction of these targeted drugs has significantly improved the prognosis of previously treatment resistant cancers. It is increasingly recognised that these drugs have a number of cardiovascular toxicities including left ventricular systolic dysfunction, hypertension and QTc interval prolongation. Whilst cardiotoxicity is largely reversible and manageable with medical therapy, it does limit the effective use of these highly active agents.

Keywords: BRAF inhibitors; Cardiovascular toxicity; Hypertension; Left ventricular systolic dysfunction; MEK inhibitors; Melanoma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Cardiotoxicity* / diagnosis
  • Cardiotoxicity* / etiology
  • Humans
  • Melanoma / drug therapy
  • Neoplasms / drug therapy
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Proto-Oncogene Proteins B-raf* / antagonists & inhibitors
  • Risk Assessment

Substances

  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Antineoplastic Agents