Systematic cardio-oncologic screening of patients treated with BRAF and MEK inhibitors

Abstract

BRAF and MEK inhibitors have significantly improved progression-free and overall survival compared to monotherapy, they carry a high risk of cardiovascular adverse events (CVAEs) because the MAPK pathway is also essential for normal cardiac and vascular physiology. The ESC Guidelines on Cardio-Oncology recommend a risk-adapted strategy but real-world data on consistent population are scarce. Aim of the present study is to assess the real prevalence of CV complications in BRAFi/MEKi treated patients and compare CV toxicity between the Trametinib + Dabrafenib doublet and the other ones in a contemporary cohort of real-world patients. Prospective, observational study enrolling all consecutive patients referred to our Regional Cardio-Oncology Service for baseline evaluation before starting BRAFi/MEKi therapy from 2019 to 2025. Monitoring included serial echocardiography blood pressure monitoring, ECGs and biomarkers at baseline, 4 weeks, and 3-monthly intervals for at least 12 months. Outcomes of interest include new diagnosis of arterial hypertension, LV systolic dysfunction, worsened symptoms of heart failure and new occurrence of arrhythmias. 50 patients were consecutively enrolled and followed up for at least 12 months. The wast majoirity of patients (82%) had a low HFA-ICOS risk profile at baseline and 84% were subsequently treated with Trametinib + Dabrafenib. During follow-up, 18% had a new diagnosis of arterial hypertension and were subsequently treated, 12% had a significant reduction of LV ejection fraction (either <50% or a reduction of 10% or more from the baseline), 20% reported a worsening of at least one functional class, 4% had at least one episode of atrial fibrillation and 2% had a PM implanted for advanced AV block. Figure 1 details the relative prevalence of CV events according to BRAFi/MEKi doublets. Despite a predominantly low HFA-ICOS risk profile, nearly one-fifth of patients in this contemporary cohort developed significant cardiovascular complications, including symptomatic heart failure and new-onset arrhythmias. Consequently, a proactive and multidisciplinary monitoring strategy is mandatory for all patients receiving BRAFi/MEKi doublets to ensure early detection and prompt management of toxicities, regardless of their initial risk category.CV complications according to BRAFi/MEKi