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

Introduction BRAF and MEKis have revolutionized the management of BRAF V600-mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF-D) related to these treatments has not been thoroughly evaluated to date. Purpose The main objective of this study was to describe characteristics of LVEF-D in melanoma patients treated with BRAF and/or MEKis. Methods Metastatic melanoma patients treated with BRAF and/or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (XXX University Hospital, XXX). LVEF-D was defined as a reduction in LVEF310 % from baseline to a value Results Among the 88 patients included, 12 (13.6 %) experienced a LVEF-D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months [IQR (3–21)]. No patient previously treated with beta-blockers (N = 12) experienced a LVEF-D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow-up did not find any predictive marker of LVEF-D. All patients who benefited from a specific treatment of LVEF-D had a normalization of LVEF at the end of follow-up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta-blockers than those who did not (P = 0.019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF-D (P = 0.006) and the latter did not influence overall-survival (P = 0.117) or progression-free-survival (P = 0.297). Conclusion LVEF-D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF-D occurs.