Shen Jun, Luo Pingli, Xu Jianmei
Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, #3 East Qingchun Road, Hangzhou, Zhejiang 310016, China.
Ther Adv Drug Saf. 2024 Sep 24;15:20420986241278498. doi: 10.1177/20420986241278498. eCollection 2024.
Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are targeted therapies designed to selectively block CDK4/6, crucial regulators of the cell cycle. These inhibitors play a pivotal role in restoring cell cycle control, particularly in breast cancer cases marked by abnormal CDK regulation, ultimately inhibiting uncontrolled cell division and tumor growth.
This analysis aimed to comprehensively examine adverse effects in CDK4/6 inhibitors using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.
Disproportionality analysis was conducted to analyze the adverse event (AE) reports related to CDK4/6 inhibitor submitted to the FAERS database.
We collected AE reports regarding palbociclib, ribociclib, abemaciclib, trilaciclib, and dalpiciclib submitted to the FAERS from 2015Q1 to 2023Q1. We used the system organ class and the Standardized MedDRA Query to perform a comprehensive search for AEs at the preferred term (PT) level, using case reports as our data source. After removing duplicate reports, we performed disproportionality analysis and sensitivity analysis to identify safety signals.
A total of 85,635 reports encompassing 280,211 AEs were extracted for analysis. Among 3681 scrutinized PTs, approximately 484 were detected as statistically significant signals associated with CDK4/6 inhibitors. It was noteworthy that palbociclib and ribociclib had comparable safety profiles, whereas abemaciclib exhibited distinctive safety patterns. Notably, our analysis found novel safety signals linked to CDK4/6 inhibitors, including nail-related disorders such as onychoclasis, nail disorder, and nail discoloration, and psychiatric concerns, including eating disorders and emotional disorder.
Overall, the present study identified several new safety signals of CDK4/6 inhibitors, as well as differences among various drugs within the CDK4/6 category, through the use of the FDA FAERS, which deserve more careful monitoring in the clinic.
细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂是旨在选择性阻断CDK4/6的靶向疗法，CDK4/6是细胞周期的关键调节因子。这些抑制剂在恢复细胞周期控制中起关键作用，特别是在以CDK调节异常为特征的乳腺癌病例中，最终抑制不受控制的细胞分裂和肿瘤生长。
本分析旨在使用美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库全面检查CDK4/6抑制剂的不良反应。
进行不成比例分析，以分析提交至FAERS数据库的与CDK4/6抑制剂相关的不良事件（AE）报告。
我们收集了2015年第一季度至2023年第一季度提交至FAERS的关于哌柏西利、瑞博西尼、阿贝西利、曲拉西利和达尔西利的AE报告。我们使用系统器官分类和标准化医学术语词典查询，以病例报告作为数据源，在首选术语（PT）级别对AE进行全面搜索。去除重复报告后，我们进行不成比例分析和敏感性分析以识别安全信号。
共提取85635份报告，涵盖280211例AE用于分析。在3681个经过仔细审查的PT中，约484个被检测为与CDK4/6抑制剂相关的具有统计学意义的信号。值得注意的是，哌柏西利和瑞博西尼具有相似的安全性，而阿贝西利表现出独特的安全模式。值得注意的是，我们的分析发现了与CDK4/6抑制剂相关的新的安全信号，包括与指甲相关的疾病，如甲剥离、指甲疾病和指甲变色，以及精神方面的问题，包括饮食失调和情绪障碍。
总体而言，本研究通过使用FDA的FAERS确定了CDK4/6抑制剂的几个新的安全信号，以及CDK4/6类别内各种药物之间的差异，这些在临床上值得更密切的监测。
