Prospective Evaluation of the Cardiovascular Effects of BRAF and MEK Inhibitors in Patients With Melanoma.

Abstract

Background: Rapidly accelerated fibrosarcoma B-type (BRAF) and MEK inhibitors have revolutionized outcomes for patients with BRAF-mutated melanoma. However, they are associated with cardiovascular adverse effects. The real-world incidence and risk factors for these effects are poorly described.

Objectives: The aim of this study was to characterize the incidence and risk factors for BRAF inhibitor- and MEK inhibitor-associated hypertension and cancer therapy-related cardiac dysfunction (CTRCD) in a real-world setting.

Methods: A prospective, longitudinal, cohort study was undertaken among patients with melanoma treated with BRAF and MEK inhibitors in a regional cancer network (March 2021 to March 2023). Baseline cardiotoxicity risk stratification was assessed using the European Society of Cardiology cardio-oncology guideline-recommended tool. Comprehensive cardiovascular assessment was performed at baseline and at 4, 12, and 24 weeks, including home and clinic blood pressure, echocardiography, stress perfusion cardiovascular magnetic resonance imaging and blood biomarkers. CTRCD was defined using International Cardio-Oncology Society definitions.

Results: A total of 61 participants were enrolled. Twenty-eight participants (45.9%) developed hypertension and 45.9% developed CTRCD: 24 (85.7%) mild, 3 (10.7%) moderate, and 1 (3.6%) severe. All moderate or severe CTRCD was evident by 4 weeks and at least partially reversible. No patient at low baseline risk developed moderate or severe CTRCD. Patients with CTRCD had higher median baseline N-terminal pro-B-type natriuretic peptide compared with those without (109 pg/mL [Q1-Q3: 51-380 pg/mL] vs 54 pg/mL [Q1-Q3: 29-149 pg/mL]; P = 0.047). There were no robust associations between hypertension nor cardiovascular magnetic resonance imaging-derived myocardial or perfusion characteristics and incident CTRCD.

Conclusions: BRAF inhibitor- and MEK inhibitor-associated hypertension and CTRCD are common. The present results reinforce the utility of baseline cardiotoxicity risk stratification, including assessment of N-terminal pro-B-type natriuretic peptide. Future guidelines should consider recommending early surveillance echocardiography for higher risk patients.