CDK4/6抑制剂联合内分泌药物治疗HR阳性/HER2阴性乳腺癌疗效与安全性的Meta分析

Meta-analysis of efficacy and safety of CDK4/6 inhibitor combined with endocrine in the treatment of HR^(+)/HER2^(-) breast cancer

目的 评价4种周期蛋白依赖性激酶4/6(CDK4/6)抑制剂(达尔西利、阿贝西利、瑞波西利、哌柏西利)联合内分泌药物治疗激素受体(HR)阳性/人表皮生长因子受体2(HER2)阴性乳腺癌的疗效和安全性。方法 计算机检索PubMed、the Cochrane Library、Web of Science、Embase、中国知网、万方数据、维普网,收集CDK4/6抑制剂联合内分泌药物(试验组)对比单用内分泌药物或联用安慰剂(对照组)的随机对照试验(RCT),检索时限为建库至2023年4月。筛选文献、数据提取和质量评价后,采用RevMan 5.4.1软件进行Meta分析。结果 共纳入22篇文献,涉及15项RCT,合计18 574例患者。Meta分析结果显示,试验组患者的无进展生存期[HR=0.77,95%CI(0.74,0.79),P<0.000 01]、总生存期[HR=0.91,95%CI(0.87,0.94),P<0.000 01]、客观缓解率[OR=1.71,95%CI(1.51,1.93),P<0.000 01]、临床获益率[OR=1.73,95%CI(1.52,1.95),P<0.000 01]均显著优于对照组。试验组患者的≥3级不良反应[OR=10.28,95%CI(6.97,15.17),P<0.000 01]、中性粒细胞减少[OR=65.09,95%CI(36.43,116.31),P<0.000 01]、白细胞减少[OR=22.90,95%CI(15.40,34.04),P<0.000 01]、贫血[OR=5.71,95%CI(4.51,7.22),P<0.000 01]、腹泻[OR=3.00,95%CI(1.19,7.51),P<0.05]、恶心[OR=1.99,95%CI(1.52,2.60),P<0.00001]发生率均显著高于对照组。结论CDK4/6抑制剂联合内分泌药物治疗HR阳性/HER2阴性乳腺癌的疗效显著,不良反应发生率较高,尤其是血液毒性反应。

OBJECTIVE To evaluate the efficacy and safety of four cyclin-dependent kinase 4/6(CDK4/6)inhibitors(dalpicilib,abemacilib,ribocilib,palbocilib)combined with endocrine drugs in the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR^(+)/HER2^(-))breast cancer.METHODS Computer searches were conducted on PubMed,the Cochrane Library,Web of Science,Embase,CNKI,Wanfang data and VIP to collect randomized controlled trials(RCTs)about CDK4/6 inhibitors combined with endocrine drugs(trial group)versus endocrine drugs alone or combined with placebo(control group).The search period was from the establishment of the database to April 2023.After literature screening,data extraction and quality evaluation,a meta-analysis was conducted by using RevMan 5.4.1 software.RESULTS A total of 22 articles were included,involving 15 RCTs with a total of 18574 patients.The meta-analysis results showed that the progression free survival[HR=0.77,95%CI(0.74,0.79),P<0.0001],overall survival[HR=0.91,95%CI(0.87,0.94),P<0.00001],objective response rate[OR=1.71,95%CI(1.51,1.93),P<0.00001]and clinical benefit rate[OR=1.73,95%CI(1.52,1.95),P<0.00001]of the trial group were significantly better than control group.The incidence of adverse drug reactions≥3 levels[OR=10.28,95%CI(6.97,15.17),P<0.00001],neutropenia[OR=65.09,95%CI(36.43,116.31),P<0.00001],leukopenia[OR=22.90,95%CI(15.40,34.04),P<0.00001],anemia[OR=5.71,95%CI(4.51,7.22),P<0.00001],diarrhea[OR=3.00,95%CI(1.19,7.51),P<0.05]and nausea[OR=1.99,95%CI(1.52,2.60),P<0.00001]in the trial group was significantly higher than control group.CONCLUSIONS The combination of CDK4/6 inhibitors and endocrine drugs has a significant effect on HR+/HER2-breast cancer,with a high incidence of adverse reactions,especially hematotoxicity.