Cardiotoxicity in metastatic melanoma patients treated with BRAF and MEK inhibitors in a real-world setting

• Published in: Acta oncologica 2022-01, Vol.61 (1), p.45-51
• Main Authors: Pedersen, Sidsel, Larsen, Kirstine Ostenfeld, Christensen, Alex Hørby, Svane, Inge Marie, Zerahn, Bo, Ellebaek, Eva
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols; BRAF/MEK inhibition; cardiotoxicity; Cardiotoxicity - etiology; equilibrium radionuclide angiography; Humans; malignant melanoma; Melanoma - drug therapy; Mitogen-Activated Protein Kinase Kinases - therapeutic use; multigated acquisition; Protein Kinase Inhibitors - adverse effects; Proto-Oncogene Proteins B-raf - genetics; Retrospective Studies; Skin Neoplasms - drug therapy; Stroke Volume; Ventricular Function, Left
• ISSN: 0284-186X; 1651-226X
• DOI: 10.1080/0284186X.2021.1992010

Combination therapy with BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved the outcome for patients with BRAF-mutated melanoma. A reduction in left ventricular ejection fraction (LVEF) is a known side effect during treatment with BRAF/MEKi. This study aimed to analyze sequential multigated acquisition (MUGA) scans for the evaluation of LVEF and provide real-world data on cardiotoxicity induced by BRAF/MEKi in advanced melanoma. All patients with advanced melanoma treated with dabrafenib and trametinib at Herlev and Gentofte Hospital, Denmark, between March 2015 and September 2019, were included retrospectively. MUGA scans performed at baseline and every three months during treatment were analyzed. Cardiotoxicity was defined as a decline of ≥10 percentage point (pp) to an LVEF 50% (minor cardiotoxicity). A total of 139 patients were included. Forty-six patients (33%) met our criteria for cardiotoxicity; 31 patients (22%) experienced minor cardiotoxicity and 15 patients (11%) experienced major cardiotoxicity. Median time to decline in LVEF was 94 days, and all clinically significant declines in LVEF occurred before evaluation at six months. Reversibility of LVEF was seen in 80% of patients, three patients were not evaluable for reversibility. A low left ventricular peak emptying rate adjusted for heart rate (LVPERadj) at baseline was found a potential risk factor for the development of major cardiotoxicity (RR = 0.159, p = 0.001). A decline in LVEF is common for patients with advanced melanoma treated with BRAF/MEKi but rarely clinically significant. No significant decline in LVEF was observed after evaluation at six months, therefore routine monitoring of LVEF might be stopped after six to nine months of BRAF/MEKi therapy. A low LVPERadj might be a risk factor for the development of cardiotoxicity and is suggested for further investigation.