激素受体阳性、人表皮生长因子受体2阴性转移性乳腺癌女性患者中CDK4/6抑制剂与PI3K/AKT/mTOR抑制剂的比较：28项随机对照试验的最新系统评价和网状Meta分析
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.
作者信息
Xu Hangcheng, Wang Yan, Han Yiqun, Wu Yun, Wang Jiayu, Xu Binghe
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Front Oncol. 2022 Aug 24;12:956464. doi: 10.3389/fonc.2022.956464. eCollection 2022.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022321172.
背景
需要更新证据来比较细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂与磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）抑制剂对激素受体阳性且人表皮生长因子受体2阴性转移性乳腺癌患者的疗效和安全性。
方法
利用来自包含CDK4/6抑制剂或PI3K/AKT/mTOR抑制剂干预措施的随机对照试验（RCT）数据进行系统评价和网状Meta分析。无进展生存期（PFS）、总生存期（OS）和治疗相关不良事件（TRAEs）是主要关注的结局指标。合并风险比（HRs）和比值比（ORs）以及95%可信区间（CrIs）分别用于评估生存结局和安全性概况。
结果
共纳入28项RCT，涉及12129名参与者。汇总分析表明，CDK4/6抑制剂比PI3K/AKT/mTOR抑制剂显著延长PFS（HR，0.81；95%CrI，0.69 - 0.94），而在OS方面未检测到显著差异。在平衡治疗线数和转移部位后，CDK4/6抑制剂的优势仅在内脏和非内脏亚组中出现。在CDK4/6抑制剂中，阿贝西利在≥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）。不同种类的PI3K/AKT/mTOR抑制剂中口腔炎和消化系统疾病的发生率不同。不同干预措施在肝毒性、腹泻和高血糖的TRAEs方面存在差异。
结论
CDK4/6抑制剂在PFS方面显示出更好的疗效，但考虑治疗线数时益处消失。在两类药物中发现了特定且不同的安全性概况。
系统评价注册
Zotero 插件