CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials.
CDK4/6 inhibitors versus PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: An updated systematic review and network meta-analysis of 28 randomized controlled trials.
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DOI：
10.3389/fonc.2022.956464
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发表时间：
2022
影响因子：
4.7
通讯作者：
Xu, Binghe
中科院分区：
文献类型：
--
作者：
Xu, Hangcheng;Wang, Yan;Han, Yiqun;Wu, Yun;Wang, Jiayu;Xu, Binghe
关键词：
需要更新证据以比较细胞周期蛋白依赖性激酶4和6（CDK 4/6）抑制剂与磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂治疗激素受体阳性和HER 2阴性转移性乳腺癌患者的疗效和安全性。使用包含CDK 4/6抑制剂或PI 3 K/AKT/mTOR抑制剂干预的随机对照试验（RCT）的数据进行了系统性综述和网络荟萃分析。无进展生存期（PFS）、总生存期（OS）和治疗相关不良事件（TRAE）是关注的主要结局。合并的风险比（HR）和比值比（OR）以及95%可信区间（CrIs）分别用于评估生存结局和安全性特征。共纳入28项RCT，12，129例受试者。汇总分析显示，CDK 4/6抑制剂比PI 3 K/AKT/mTOR抑制剂显著延长PFS（HR，0.81; 95% CrI，0.69-0.94），而OS方面未检测到显著差异。在平衡治疗线和转移部位后，CDK 4/6抑制剂的优效性仅出现在内脏和非内脏亚组中。在CDK 4/6抑制剂中，abemaciclib在≥3级中性粒细胞减少方面显著优于其他药物（OR，0.04; 95% CrI，0.01-0.15）。不同PI 3 K/AKT/mTOR抑制剂的口腔炎和消化系统疾病的发生率不同。在不同干预措施中，肝毒性、腹泻和高血糖的TRAE出现不一致。CDK 4/6抑制剂在PFS中显示出更好的疗效，但考虑到治疗线时，获益消失。在两类药物中发现了特异性和不一致的安全性特征。 ，标识符CRD 42022321172。
Updated evidence was required to compare the efficacy and safety of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors for patients with hormone receptor-positive and HER2-negative metastatic breast cancer. A systematic review and network meta-analysis was conducted utilizing data from randomized controlled trials (RCTs) that contained interventions of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were primary outcomes of interest. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% credible intervals (CrIs) were used to assess the survival outcomes and safety profiles, respectively. A total of 28 RCTs with 12,129 participants were included. Pooled analysis showed that CDK4/6 inhibitors significantly prolonged PFS than PI3K/AKT/mTOR inhibitors (HR, 0.81; 95% CrI, 0.69–0.94), whereas no significant differences were detected regarding OS. After balancing the treatment lines and metastatic sites, the superiority of CDK4/6 inhibitors only appeared in the visceral and non-visceral subgroups. Among CDK4/6 inhibitors, abemaciclib was significantly better than others in ≥3 grade neutropenia (OR, 0.04; 95% CrI, 0.01–0.15). The incidence of stomatitis and digestive disorders was different among diverse kinds of PI3K/AKT/mTOR inhibitors. Discrepancies appeared regarding TRAEs of hepatotoxicity, diarrhea, and hyperglycemia among different interventions. CDK4/6 inhibitors showed better efficacy in PFS, but the benefits disappeared when taking treatment line into consideration. Specific and discrepant safety profiles were found in two categories of agents. , identifier CRD42022321172.
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DOI：
10.1016/j.annonc.2020.10.596
发表时间：
2021-03
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Dent S;Cortés J;Im YH;Diéras V;Harbeck N;Krop IE;Wilson TR;Cui N;Schimmoller F;Hsu JY;He J;De Laurentiis M;Sousa S;Drullinsky P;Jacot W
通讯作者：
Jacot W
影响因子：
45.3
作者：
Bachelot, Thomas;Bourgier, Celine;Pujade-Lauraine, Eric
通讯作者：
Pujade-Lauraine, Eric
影响因子：
50.5
作者：
Hortobagyi, G. N.;Stemmer, S. M.;O'Shaughnessy, J.
通讯作者：
O'Shaughnessy, J.
影响因子：
51.1
作者：
Finn, Richard S.;Crown, John P.;Slamon, Dennis J.
通讯作者：
Slamon, Dennis J.
影响因子：
5.2
作者：
Elfgen C;Bjelic-Radisic V
通讯作者：
Bjelic-Radisic V