使用CDK4/6抑制剂的肝脏不良事件:结合元分析和FAERS数据库的系统综述
Yuyao Tang1, Yongxin Li1, Chengrong Zhang1
1Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China.
Expert opinion on drug safety
|February 17, 2025
概括
细胞周期蛋白依赖性激酶4和6抑制剂 (CDK4/6is) 会增加乳腺癌患者肝脏毒性的风险. 与dalpiciclib不同的是,Palbociclib,ribociclib和abemaciclib与显著的肝毒性有关.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 细胞周期蛋白依赖性激酶4和6抑制剂 (CDK4/6is) 与内分泌疗法 (ET) 结合,是标准的乳腺癌 (BC) 治疗方法.
- CDK4/6与各种副作用有关,包括潜在的肝毒性.
- 了解CDK4/6的肝毒性特异性风险对于患者管理至关重要.
研究的目的:
- 为了研究CDK4/6抑制剂与乳腺癌患者肝毒性之间的关联.
- 为了比较不同CDK4/6抑制剂的肝毒性潜力.
- 为了确定与这些药物相关的肝损伤的特定模式.
主要方法:
- 在PubMed,Embase和Cochrane图书馆数据库中进行系统的文献搜索,截至2024年3月31日.
- 包括20项随机对照试验 (RCT),涉及24,342名乳腺癌患者.
- 分析了400个来自FDA不良事件报告系统 (FAERS) 的病例,使用固定效应,随机效应和报告几率比率 (ROR) 模型.
主要成果:
- CDK4/6 抑制剂与肝毒性显著相关 (OR = 1.76,95% CI 1.40-2.22).
- 帕尔博西基利布,里博西基利布和阿贝马西基利布显示出显著的肝毒性,而达尔皮西基利布则没有.
- FAERS数据显示,利博西基利布和阿贝马西基利布的肝酶和器官毒性信号,但不是palbociclib.
结论:
- CDK4/6抑制剂提高了乳腺癌患者肝毒性风险.
- 帕尔博西基利布,里博西基利布和阿贝马西基利布与肝损伤有关,主要表现为ALT和AST水平升高.
- 与其他CDK4/6抑制剂相比,dalpiciclib似乎具有较低的肝毒性风险概况.
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