Ding Haiying, Xu Weiben, Dai Mengfei, Li Shujing, Xin Wenxiu, Tong Yinghui, He Chaoneng, Mi Xiufang, Zhan Zhajun, Fang Luo
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
Expert Opin Drug Saf. 2025 Feb;24(2):157-165. doi: 10.1080/14740338.2024.2348566. Epub 2024 May 16.
We aimed to evaluate and compare the risk of hematological adverse events (AEs) associated with CDK4/6 inhibitors using data from randomized controlled trials (RCTs) and Food and Drug Adverse Event Reporting System (FAERS) database.
The PubMed, Embase, and Cochrane Library databases were searched for RCTs related to abemaciclib, palbociclib, and ribociclib. A network meta-analysis (NMA) was conducted to compare the risks of hematological AEs, and a disproportionality analysis was performed to detect signals of hematological AEs.
16 RCTs comprising 16,350 breast cancer patients were included. Palbociclib and ribociclib had similar risks for hematological AEs, except a higher risk of grade 3-4 leukopenia observed with palbociclib (risk ratio [RR]: 7.84, 95% confidence interval [95%CI]: 1.33-41.28). Abemaciclib had a higher risk of anemia than both ribociclib (grade 1-4: RR: 2.23, 95% CI: 1.25 - 3.96; grade 3-4: RR: 3.52, 95% CI: 1.59 - 8.11) and palbociclib (grade 1-4: RR: 1.65, 95%CI: 1.03 - 2.59), but a lower risk of grade 3-4 of both leukopenia (RR: 0.12, 95%CI: 0.02 - 0.49) and neutropenia (RR: 0.15, 95%CI: 0.04 - 0.52) compared with palbociclib. Signals indicating occurrence of leukopenia, neutropenia, anemia, and thrombocytopenia were identified for three CDK4/6 inhibitors.
Abemaciclib, palbociclib, and ribociclib showed significant but inconsistent hematological toxicity risks.
我们旨在利用随机对照试验（RCT）数据和食品药品不良事件报告系统（FAERS）数据库，评估和比较与细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂相关的血液学不良事件（AE）风险。
检索PubMed、Embase和Cochrane图书馆数据库，查找与阿贝西利、哌柏西利和瑞博西尼相关的RCT。进行网络荟萃分析（NMA）以比较血液学AE的风险，并进行不成比例分析以检测血液学AE的信号。
纳入了16项RCT，共16350例乳腺癌患者。哌柏西利和瑞博西尼的血液学AE风险相似，但哌柏西利观察到3-4级白细胞减少的风险更高（风险比[RR]：7.84，95%置信区间[95%CI]：1.33-41.28）。阿贝西利的贫血风险高于瑞博西尼（1-4级：RR：2.23，95%CI：1.25-3.96；3-4级：RR：3.52，95%CI：1.59-8.11）和哌柏西利（1-4级：RR：1.65，95%CI：1.03-2.59），但与哌柏西利相比，3-4级白细胞减少（RR：0.12，95%CI：0.02-0.49）和中性粒细胞减少（RR：0.15，95%CI：0.04-0.52）的风险较低。确定了三种CDK4/6抑制剂出现白细胞减少、中性粒细胞减少、贫血和血小板减少的信号。
阿贝西利、哌柏西利和瑞博西尼显示出显著但不一致的血液学毒性风险。
