Cardiotoxicity of BRAF/MEK inhibitors: a longitudinal study incorporating contemporary definitions and risk scores

Glen, C., Adam, S., McDowell, K., Waterston, A., Tan, Y. Y., Petrie, M. C. , Coats, C. J. and Lang, N. N. (2023) Cardiotoxicity of BRAF/MEK inhibitors: a longitudinal study incorporating contemporary definitions and risk scores. JACC: CardioOncology, (doi: 10.1016/j.jaccao.2023.04.004) (In Press)

[img] Text
296246.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

Abstract

Background: Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized treatment for patients with BRAF-mutated melanoma. Although left ventricular systolic dysfunction associated with these therapies has been reported in clinical trials, the real-world incidence is poorly defined, as are risk factors for its development. Objectives: This study sought to characterize the incidence, time course, and risk factors for cancer therapy–related cardiac dysfunction (CTRCD) in patients with melanoma receiving BRAF and MEK inhibitors. Methods: Patients with melanoma treated with BRAF and MEK inhibitors at a cancer hospital network between June 1, 2017, and June 30, 2020, were included retrospectively. CTRCD was defined as mild, moderate, or severe according to International Cardio-Oncology Society (ICOS) definitions. Baseline cardiotoxicity risk stratification was performed using the Heart Failure Association/ICOS tool. Results: Of the 63 patients included, 27% developed CTRCD (17% mild and 10% moderate). No patients developed severe CTRCD or symptomatic heart failure. CTRCD occurred most frequently in patients considered to be at “low” and “medium” baseline risk of cardiotoxicity (82%). The baseline left ventricular ejection fraction and global longitudinal strain were not different in patients who developed moderate CTRCD vs those who did not. Left ventricular internal diameters in diastole and systole were larger in patients who developed moderate CTRCD compared with those who did not (left ventricular internal diameter in diastole: 4.9 ± 0.6 cm vs 4.3 ± 0.6 cm; P = 0.023; left ventricular internal diameter in systole: 3.3 ± 0.4 cm vs 2.8 ± 0.5 cm; P = 0.039). Conclusions: BRAF and MEK inhibitor–associated CTRCD is common. The utility of the Heart Failure Association/ICOS risk stratification tool appears limited in this group, and better risk prediction tools are needed. The long-term consequences of CTRCD, particularly mild CTRCD, warrant evaluation in larger prospective studies.

Item Type:Articles
Additional Information:NNL and CG are supported by an unrestricted grant from Roche Diagnostics, Switzerland. NNL and MCP are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217).
Status:In Press
Refereed:Yes
Glasgow Author(s) Enlighten ID:Coats, Dr Caroline and Lang, Professor Ninian and McDowell, Dr Kirsty and Tan, Dr Yun Yi and Petrie, Professor Mark and Adam, Sarah and Glen, Dr Claire
Authors: Glen, C., Adam, S., McDowell, K., Waterston, A., Tan, Y. Y., Petrie, M. C., Coats, C. J., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:JACC: CardioOncology
Publisher:Elsevier
ISSN:2666-0873
ISSN (Online):2666-0873
Published Online:06 June 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in JACC: CardioOncology 2023
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science