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通过CDK4/6抑制剂延长QTc:随机对照试验的系统审查和元分析
Bruno Murad1, Pedro C A Reis2, Alice Deberaldini Marinho3
1Faculdade de Medicina de Barbacena (FUNJOB), Minas Gerais, Brazil.
循环素依赖激酶 (CDK) 4/6 抑制剂增加乳腺癌患者的QTc延长风险. 与palbociclib相比,ribociclib具有更高的风险,并且仅导致3级QTc延长.
科学领域:
- 心脏病学 心脏病学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 循环素依赖性激酶 (CDK) 4/6 抑制剂对于治疗ER+/HER2-乳腺癌至关重要.
- 这些抑制剂表现出不同的化学,生物和药理学特征,包括不同的毒性.
- 有关QTc延长作为CDK4/6抑制剂的潜在不良影响存在担忧.
研究的目的:
- 调查QTc延长是否是CDK4/6抑制剂的一般副作用,还是特定于ribociclib.
- 为了比较不同CDK4/6抑制剂之间的QTc延长风险.
主要方法:
- 在PubMed,Embase和Cochrane图书馆系统搜索相关的随机对照试验 (RCT).
- 纳入标准:RCT比较HR+乳腺癌患者中使用CDK4/6抑制剂治疗的QTc延长患病率与那些不使用这些抑制剂的患者.
- 聚合相对风险 (RR) 和平均差异 (MD) 与95%的置信区间 (CI) 计算了QTc延长.
主要成果:
- 包括14个RCT,包括16196名患者 (8,576名CDK4/6i).
- CDK4/6抑制剂显著增加了QTc延长的风险 (RR = 2.35,P < .001).
- 亚组分析显示,利博西基利布 (RR = 3.12,P < .001) 和palbociclib (RR = 1.51,P = .025) 的QTc间隔都增加了,而利博西基利布显示出更高的风险.
结论:
- 利博西基利布和帕尔博西基利布都与QTc延长有关.
- 利博西克利布对QTc延长的风险量较高,并且仅与3级事件有关.
- 这些发现有助于就CDK4/6抑制剂的安全性进行临床决策.
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