基于FAERS数据库的周期蛋白依赖性激酶4/6抑制剂血液毒性真实世界研究

Real-World Study on Hematological Toxicities of Cyclin-dependent Kinase 4/6 InhibitorsBased on FAERS Database

目的 基于美国美国食品药品管理局(FDA)的不良事件报告系统(FAERS)分析3种周期蛋白依赖性激酶4/6(CDK4/6)抑制剂上市后的不良事件(AEs)信号,为临床用药安全提供参考。方法 提取FAERS数据库2015年第一季度至2022年第一季度共29个季度AEs,利用报告比值比法(ROR)和比例报告比值法(PRR)对CDK4/6抑制剂AEs进行数据挖掘。结果 CDK4/6抑制剂相关性血液毒性报告共有7 872份,各抑制剂血液毒性AEs占总AEs比例依次为哌柏西利(80.31%)>瑞博西利(15.36%)>阿贝西利(4.33%)。血液毒性常见中性粒细胞减少和贫血。哌柏西利(2 982/6 322,47.17%)和瑞博西利(613/1 209,50.70%)致中性粒细胞减少的报告占比较阿贝西利(117/341,34.31%)更高,血液毒性主要发生在药物开始使用后60 d内(1 630,61.86%),哌柏西利中位时间最长,且用药90 d后仍有32.9%的患者存在血液毒性,不同CDK4/6抑制剂血液毒性临床表现及发生强度存在差异。结论 哌柏西利、阿贝西利、瑞博西利均会导致明显的血液毒性,其中阿贝西利致血液毒性报告最少,但要警惕阿贝西利致贫血后导致死亡的风险。用药后的2个月内密切监测全血细胞计数,关注中性粒细胞、血红蛋白等水平,警惕CDK4/6抑制剂相关血液AEs的发生。

Objective To evaluate adverse events(AEs)of hematological toxicities in cyclin-dependent kinase 4/6(CDK4/6)inhibitors based on the FDA adverse event reporting system(FAERS)database,and to provide a reference for rational drug use in the clinic.Methods A total of 29 quarterly AEs were extracted from the FAERS database from January 2015 to March 2022.Reported odds ratio(ROR)and proportional reported ratio(PRR)were used for data mining of CDK4/6 inhibitor AEs.Results A total of 7872 AEs related to CDK4/6 inhibitors were reported,and the proportion of hematological AEs of each inhibitor was palbociclib(80.31%),ribociclib(15.36%),and abemaciclib(4.33%).Neutropenia and anemia were common in hematological toxicities.Palbociclib(2982/6322,47.17%)and ribociclib(613/1209,50.70%)caused more neutropenia than abemaciclib(117/341,34.31%).Hematological toxicities mainly occurred 60 days after drug initiation(1630,61.86%).Palbociclib had the longest median onset time,and 32.9%of patients still had hematological toxicities after 90 days of treatment.The clinical features and intensity were different among CDK4/6 inhibitors.Conclusions Palbociclib,abemaciclib,and ribociclib all cause significant hematological toxicities,among which abemaciclib has fewest reports of hematological toxicities.Still,the risk of death after anemia caused by abemaciclib should be noted.Complete blood cell count should be closely monitored within the first two months after treatment to monitor the patient's neutrophils and hemoglobin.The occurrence of hematological AEs associated with CDK4/6 inhibitors should be noted in the clinic.