Cyclin‐dependent kinase 4/6 inhibitors and cardiotoxic events in breast cancer: A pharmacovigilance study based on the FAERS database

作者：Ting Li, Miaomiao Zhang, Tian Zhang, Shaoqiang Li, Chen Kou, Ming Zhao, Jing Huang, Weihang Cao, Pengfei Jin · 发表于：International Journal of Cancer · 年份：2024 · DOI：10.1002/ijc.35255 · 被引用次数：8 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、Cancer-related cognitive impairment studies

Recent trials have highlighted the cardiotoxicity of ribociclib, a CDK4/6 inhibitor, particularly its association with QT prolongation. However, studies on the link between CDK4/6 inhibitors and cardiotoxic events show inconsistent results, and the factors influencing these events and related drug interactions remain underexplored. To address these uncertainties, our study utilizes the FDA adverse event reporting system database (Q1 2015 to Q1 2024) to examine the cardiotoxic events of CDK4/6 inhibitors in breast cancer patients. We employed a comprehensive analytical framework, applying disproportionality methods including Bayesian confidence propagation neural network, proportional reporting ratio, and reporting odds ratio. Our findings highlight significant variability in cardiotoxic events among different CDK4/6 inhibitors, with ribociclib (IC: 0.26, 95%CI: 0.18-0.34) exhibiting pronounced cardiotoxicity. Notably, ribociclib was associated with serious cardiotoxic events such as torsade de pointes/QT prolongation (IC: 2.11, 95% CI: 1.90-2.29) and conduction defects (IC: 2.07, 95% CI: 1.87-2.23). For the first time, palbociclib has been identified with positive signals for cardiotoxic events at the preferred terms level, including pulmonary oedema, increased blood pressure, myocardial infarction, and cardiac flutter. Moreover, multivariable logistic regression and Bayesian network analyses reveal that age, geographic location, and the number of concomitant medications sign...