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Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: A

Mathilde Berger1, Mona Amini-Adlé1, Delphine Maucort-Boulch2,3

  • 1Service de dermatologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France.

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|February 15, 2020
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Summary

BRAF and MEK inhibitors can cause left ventricular ejection fraction decrease (LVEF-D) in melanoma patients. This manageable side effect is linked to ocular toxicity and improves with specific treatments like beta-blockers.

Keywords:
BRAF inhibitorMEK inhibitoradverse eventscardiac toxicityheart failureleft ventricular ejection fractionleft ventricular systolic dysfunctionmetastatic melanoma

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Area of Science:

  • Cardiology
  • Oncology
  • Pharmacology

Background:

  • BRAF and MEK inhibitors (MEKis) have transformed BRAFV600-mutated melanoma treatment.
  • Left ventricular ejection fraction decrease (LVEF-D) is a potential adverse event of these therapies, requiring thorough evaluation.

Purpose of the Study:

  • To characterize LVEF-D in melanoma patients receiving BRAF and/or MEK inhibitors.
  • To identify predictors and outcomes of LVEF-D in this patient population.

Main Methods:

  • Retrospective analysis of 88 metastatic melanoma patients treated with BRAF and/or MEKis (March 2012-May 2018).
  • LVEF-D defined as LVEF reduction ≥10% from baseline to <55%; normalization as LVEF ≥55%.

Main Results:

  • 13.6% of patients experienced LVEF-D (median onset 11 months).
  • No LVEF-D observed in patients pre-treated with beta-blockers.
  • LVEF normalized in all patients receiving specific LVEF-D treatment; recovery was better with ACE inhibitors and beta-blockers (P=.019).
  • Ophthalmological adverse events were more frequent in patients with LVEF-D (P=.006).
  • LVEF-D did not impact overall-survival or progression-free-survival.

Conclusions:

  • LVEF-D is a common, manageable side effect of BRAF/MEK inhibitors in melanoma.
  • LVEF-D is associated with ocular toxicity, warranting ophthalmological monitoring.
  • Cardioprotective medications, particularly beta-blockers and ACE inhibitors, may aid LVEF recovery.