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

IF 5.7 2区 医学 Q1 ONCOLOGY International Journal of Cancer Pub Date : 2024-11-13 DOI:10.1002/ijc.35255
Ting Li, Miaomiao Zhang, Tian Zhang, Shaoqiang Li, Chen Kou, Ming Zhao, Jing Huang, Weihang Cao, Pengfei Jin
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Abstract

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 significantly influence cardiotoxic events. Our study also highlights significant drug interactions that increase the probability of specific cardiotoxic outcomes, notably with drugs like sertraline, lansoprazole, capecitabine, and torasemide. These findings highlight the need for personalized treatment plans to mitigate cardiotoxic events and improve patient safety.

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乳腺癌中的细胞周期蛋白依赖性激酶 4/6 抑制剂与心脏毒性事件:基于 FAERS 数据库的药物警戒研究。
最近的试验强调了CDK4/6抑制剂ribociclib的心脏毒性,尤其是它与QT延长的关系。然而,关于CDK4/6抑制剂与心脏毒性事件之间联系的研究结果并不一致,而且影响这些事件和相关药物相互作用的因素仍未得到充分探讨。为了解决这些不确定性,我们的研究利用 FDA 不良事件报告系统数据库(2015 年第一季度至 2024 年第一季度)来研究 CDK4/6 抑制剂在乳腺癌患者中的心脏毒性事件。我们采用了一个综合分析框架,应用了包括贝叶斯置信度传播神经网络、比例报告率和报告几率比在内的比例失调方法。我们的研究结果凸显了不同 CDK4/6 抑制剂之间心脏毒性事件的显著差异,其中利波昔布(IC:0.26,95%CI:0.18-0.34)表现出明显的心脏毒性。值得注意的是,ribociclib与严重的心脏毒性事件相关,如心动过速/QT延长(IC:2.11,95%CI:1.90-2.29)和传导缺陷(IC:2.07,95%CI:1.87-2.23)。帕博西尼(palbociclib)首次在首选术语水平上确定了心脏毒性事件的阳性信号,包括肺水肿、血压升高、心肌梗死和心扑。此外,多变量逻辑回归和贝叶斯网络分析显示,年龄、地理位置和伴随药物的数量对心脏毒性事件有显著影响。我们的研究还强调了药物间的相互作用,这种相互作用会增加特定心脏毒性结果的发生概率,特别是与舍曲林、兰索拉唑、卡培他滨和托拉塞米等药物的相互作用。这些发现凸显了个性化治疗方案的必要性,以减轻心脏毒性事件并提高患者安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
13.40
自引率
3.10%
发文量
460
审稿时长
2 months
期刊介绍: The International Journal of Cancer (IJC) is the official journal of the Union for International Cancer Control—UICC; it appears twice a month. IJC invites submission of manuscripts under a broad scope of topics relevant to experimental and clinical cancer research and publishes original Research Articles and Short Reports under the following categories: -Cancer Epidemiology- Cancer Genetics and Epigenetics- Infectious Causes of Cancer- Innovative Tools and Methods- Molecular Cancer Biology- Tumor Immunology and Microenvironment- Tumor Markers and Signatures- Cancer Therapy and Prevention
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