Sixty-four clinically relevant SDRs were identified, most of which were unexpected, including bradyarrhythmias such as QT prolongation, atrial fibrillation and disseminated intravascular coagulation with D + T, cardiac failure and pulmonary embolism with V + C. Comprehensive CV monitoring in patients receiving BRAF/MEKi therapy is fundamental to prevent or detect cAEs early and reduce treatment-related risks, particularly in high-risk populations. Here, BRAF is linked to atrial fibrillation.