CDK4/6 inhibitors and cardiovascular toxicity: Real-world evidence.

e15074 Background: Cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) have fundamentally transformed the therapeutic landscape of hormone receptor-positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer, either as monotherapy (abemaciclib) or combined with classic endocrine therapy (ribociclib, abemaciclib, and palbociclib). However, evidence regarding treatment-related cardiovascular complications, beyond the context of clinical trials, remains scarce. Methods: We retrospectively explored the FDA Adverse Events Reporting System (FAERS) to gain insight into both frequency and spectrum of cardiovascular toxicities of these novel targeted agents in real-world setting. Results: For the period January 2018 - September 2022, a total of 90,999 adverse events (AEs) in patients under CDK4/6i have been reported, with 2,739 (3.01%) and 5,176 (5.69%) records being submitted as cardiac and vascular events, respectively. The incidence of these AEs was higher in the case of ribociclib, with arrhythmia representing the main cardiac complication (512 cases), followed by palpitations (120 cases), and acute coronary syndrome (115 cases). Interestingly, there was only one report of QT prolongation; of note, ribociclib has labeling guidance for QTc assessment. Hypertension/hypertensive crisis (302 cases), flushing (251 cases), and thrombotic events (226 cases) -with the exception of pulmonary embolism which was categorized as respiratory AE- comprised the foremost vascular toxicities associated with ribociclib. Conclusions: FAERS displays a public, post-market safety evaluation database with reports from healthcare professionals as well as consumers, yet it may include duplicates, inaccurate information, and fails to confirm causal relationship between the AEs and the medicinal product. In the light of CDK4/6i long-term usage, pharmacovigilance studies are warranted to elucidate their potential cardiovascular hazard. [Table: see text]