Cardiac Effects of BRAF and MEK Inhibitors: Mechanisms and Clinical Management

Curr Oncol Rep. 2022 Mar;24(3):265-271. doi: 10.1007/s11912-022-01205-3. Epub 2022 Feb 1.

Abstract

Purpose of review: The identification of BRAF mutation prompted the development of new class of targeted therapy for treating melanoma: BRAF inhibitors and MEK inhibitors. Cardiovascular events have been reported with these treatments and could counterbalance their long-term maintenance.

Recent findings: LVEF decrease due to BRAF and MEK inhibitors appears fairly common (10%) but usually not severe, without impact on patient outcomes. To date, no treatment options have been tested to prevent or to treat a decrease of LVEF associated with BRAF and MEK inhibitors. QTc prolongation was observed in 3% and arterial hypertension in 20% during treatment but only one-third of cases required a therapeutic change. BRAF and MEK inhibitors have revolutionized the management and the prognosis of melanoma patients. Cardio-oncology units may be useful for a better care of potential cardiac toxicity and particularly to inappropriately avoid discontinuing BRAF and MEK inhibitors.

Keywords: BRAF inhibitor; Cardiac toxicity; MEK inhibitor; Melanoma.

Publication types

  • Review

MeSH terms

  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / therapeutic use
  • Mutation
  • Protein Kinase Inhibitors / adverse effects
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / genetics

Substances

  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases