Cardiovascular Risks Common With BRAF/MEK Inhibitors in Melanoma Patients
A study finds nearly half of melanoma patients receiving BRAF or MEK inhibitors develop hypertension or cardiac dysfunction. Moderate to severe cardiac issues appear within 4 weeks and only in patients with medium or higher baseline risk. Higher baseline NT-proBNP levels are associated with increased cardiac dysfunction risk.
Nearly half of patients with melanoma who received BRAF or MEK inhibitor therapy developed hypertension and/or cancer therapy–related cardiac dysfunction, according to a prospective, longitudinal cohort study published in JACC: CardioOncology. The study found that cancer therapy–related cardiac dysfunction was predominantly mild and asymptomatic, with all moderate or severe cases evident by 4 weeks of treatment initiation and seen only in patients with at least medium baseline cardiotoxicity risk.
In the analysis of 61 patients with melanoma who received BRAF or MEK inhibitor therapy in a regional cancer network, a total of 28 patients (45.9%) were diagnosed with hypertension, while an equal number developed cancer therapy–related cardiac dysfunction: 24 (85.7%) mild, 3 (10.7%) moderate, and 1 (3.6%) severe. All cases of moderate or severe cancer therapy–related cardiac dysfunction were evident by 4 weeks and were at least partially reversible. No patients classified as low risk at baseline developed moderate or severe cancer therapy–related cardiac dysfunction.
Higher baseline NT-proBNP levels appeared to be associated with incident cancer therapy–related cardiac dysfunction. Patients with vs without cancer therapy–related cardiac dysfunction had higher median baseline NT-proBNP levels (109 pg/mL vs 54 pg/mL). The investigators reported that neither hypertension nor cardiovascular MRI–derived myocardial or perfusion characteristics were robustly associated with incident cancer therapy–related cardiac dysfunction.
The investigators noted that current European Society of Cardiology cardio-oncology guidelines recommend risk stratification before the initiation of targeted therapies using the Heart Failure Association/International Cardio-Oncology Society cardiotoxicity risk tool. Routine blood pressure monitoring and electrocardiography are advised for all patients, with echocardiographic assessment of left ventricular ejection fraction tailored to baseline risk.
"Our findings support the utility of baseline cardiotoxicity risk stratification, including the measurement of NT-proBNP [N-terminal pro–B-type natriuretic peptide, identified as a potential biomarker]," as well as early echocardiographic assessment, the investigators remarked. "Serial blood pressure assessment should be performed routinely, and our findings highlight the value of home measurement."
BRAF and MEK inhibitors target the MAPK pathway—a regulator of cell proliferation, differentiation, and apoptosis—to achieve cancer disease control; however, this pathway is also involved in cardiac and vascular cell signaling, and its pharmacologic manipulation can lead to unintended cardiovascular effects. The mechanisms driving these cardiovascular toxicities remain poorly defined, and expanding clinical indications for these therapies in melanoma and other cancers further highlights the importance of understanding the mechanisms, incidence, and timing of associated cardiovascular adverse effects to inform risk stratification, surveillance, and treatment.