Cardiotoxicity following BRAF and MEK inhibitor therapy: a meta-analysis of prevalence

Background BRAF and MEK inhibition has transformed precision antineoplastic therapy for stage III/IV melanoma. Modulation of the MAPK pathway generates the potential for cardiovascular sequalae, yet the true prevalence of cardiotoxicity following BRAF/MEK therapy in real-world settings remains uncertain. Methods This meta-analysis was pre-registered on PROSPERO. Embase, Medline and Web of Science were systematically searched through December 2025 for studies longitudinally assessing cardiovascular adverse events in BRAF/MEK inhibitor recipients. Abstract screening, data extraction and quality assessment were conducted in duplicate. The primary outcome was cancer therapy related cardiac dysfunction (CTRCD), defined according to the ESC guidelines on cardio-oncology. Meta-analysis of single proportions was conducted using random-effects generalized linear mixed models with logit transformations. Between-study variance (τ2) was estimated with maximum likelihood methods. Prediction intervals (PI) indicate the anticipated variability in prevalence across different clinical settings. Results Seven studies comprising 704 BRAF/MEK inhibitor recipients (306 females, median age 61 years) were included. The majority received dabrafenib/trametinib therapy (n=393), followed by encorafenib/binimetinib (n=234), with melanoma being the underlying malignancy in most patients (96%). In terms of baseline risk (HFA-ICOS risk score), a median 46.8% of participants were considered low, 39.4% moderate, and 25.3% high risk. Three studies (n=199) recorded 48 cases of mild CTRCD with a pooled prevalence of 24% (95%CI 14-37%, 95%PI 3-78%, I2 81.2%) (Figure 1, Panel A). 76 cases of moderate CTRCD were observed in seven studies (n=704), resulting in a pooled prevalence of 10% (95%CI 6-15%, 95%PI 3-29%, I2 68.2%) (Figure 1, Panel B). Four studies (n=287) reported 5 cases of severe CTRCD with a pooled prevalence of 2% (95%CI 1-4%, 95%PI 0-7%, I2 0%) (Figure 1, Panel C). BRAF/MEK inhibitor-associated hypertension, arrhythmia and thromboembolic events occurred with a pooled prevalence of 15% (95%CI 4-41%), 4% (95%CI 1-11%) and 4% (95%CI 2-8%), respectively. Conclusion In this first quantitative synthesis of BRAF/MEK inhibitor-associated cardiotoxicity, occurrence of mild CTRCD was common (24%), while considerable proportions of patients also developed moderate (10%) and severe (2%) CTRCD. These findings underscore the need for systematic cardio-oncological surveillance following initiation of BRAF/MEK inhibitor therapy.