| アブストラクト | Introduction: The combination of BRAF and MEK inhibitors (BRAF/MEKi) has significantly improved survival in melanoma patients with BRAF V600 mutations. However, these agents can cause cardiovascular (CV) toxicity, compromising efficacy. This study evaluated the CV adverse events (cAEs) associated with BRAF/MEKi using the U.S. FDA Adverse Event Reporting System (FAERS) to identify new signals of disproportionate reporting (SDRs). Methods: Descriptive and disproportionality analyses were conducted on reports listing dabrafenib (D), vemurafenib (V), encorafenib (E), trametinib (T), cobimetinib (C), or binimetinib (B) as suspects in monotherapy or combination therapy (D + T, V + C, E + B), with melanoma as the indication and at least one cAE. Standardized MedDRA Queries (SMQs) related to cAEs, including bradyarrhythmias and tachyarrhythmias, cardiac failure, cardiomyopathy, thrombotic events, ischaemic heart disease, and myocarditis/pericarditis, were analyzed. Results: Of the 14,077,067 reports retrieved, 18,370 (0.1%) were linked to BRAF/MEKi, with 1591 (8.7%) reporting cAEs, primarily in combination therapy (n = 1268). Disproportionality analysis identified 64 clinically relevant SDRs, most of which were unexpected. Notable findings included bradyarrhythmias, such as QT prolongation with D + T (n = 59; Reporting Odds Ratio, ROR = 5.09, 95% Confidence Interval, CI = 3.94-6.58), cardiac failure with V + C (29; 3.76, 2.6-5.42), and tachyarrhythmias, particularly atrial fibrillation with D + T (99; 2.37, 1.94-2.89). Among embolic and thrombotic events, clinically significant SDRs were observed for disseminated intravascular coagulation with D + T (38; 10.22, 7.42-14.06) and pulmonary embolism with V + C (22; 2.79, 1.83-4.24). Conclusions: Our findings underscore the need for comprehensive CV monitoring in patients receiving BRAF/MEKi therapy to prevent or detect cAEs early and reduce treatment-related risks, particularly in high-risk populations. |
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| 投稿者 | Barbieri, Maria Antonietta; Russo, Giulia; Cicala, Giuseppe; Zito, Concetta; Spina, Edoardo; Silvestris, Nicola; Santarpia, Mariacarmela |
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| 組織名 | Department of Clinical and Experimental Medicine, University of Messina, 98125;Messina, Italy.;Medical Oncology Department, IRCCS Istituto Tumori "Giovanni Paolo II", 70124;Bari, Italy.;Medical Oncology Unit, Department of Human Pathology in Adulthood and Childhood;"Gaetano Barresi", University of Messina, 98125 Messina, Italy. |
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