当前位置: X-MOL 学术Curr. Probl. Cancer › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Comparative efficacy and safety of CDK4/6 and PI3K/AKT/mTOR inhibitors in women with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and network meta-analysis.
Current Problems in Cancer ( IF 2.5 ) Pub Date : 2020-05-12 , DOI: 10.1016/j.currproblcancer.2020.100606
Yiqun Han 1 , Jiayu Wang 1 , Zijing Wang 1 , Binghe Xu 1
Affiliation  

Background

CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors are both emerging agents for hormonal receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer. Evidence for the comparisons from head-to-head comparative trials is currently insufficient. This meta-analysis assessed the comparative efficacy and safety of these two groups of agents for HR+/HER2- metastatic breast cancer.

Methods

Systematic searches of PubMed, Embase, CENTRAL, SciSearch between January 2010 to December 2019 were conducted. Randomized controlled trials (RCTs) which evaluated clinical benefits and toxicities of CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy were adopted. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoint was treatment-related adverse event (TRAE). Pooled hazard ratio (HR) and risk rate (RR) were used to assess the differences between CDK4/6 and PI3K/AKT/mTOR inhibitors.

Results

A total of twenty RCTs including 9771 participants were identified in this study. Pooled results showed that PFS was considerably prolonged by targeted therapy plus endocrine therapy. PFS was relatively better in CDK4/6 inhibitors than that of PI3K inhibitor group (HR, 1.43; 95%CrI, 1.12-1.61). Similar results were demonstrated in results after balancing lines of therapy or metastatic sites, both in viscera and bone-only. Coalesced outcomes revealed that CDK4/6 inhibitors plus endocrine therapy could significantly improve OS (HR, 0.78; 95%CrI, 0.65-0.94) than PI3K/mTOR inhibitors. Safety profiles of diarrhea and rash were consistent between CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors with no difference of estimated RR. Several TRAEs signified specificity, for instance, myelosuppression in CDK4/6 inhibitors or hyperglycemia in PI3K/mTOR inhibitors.

Conclusions

Clinical efficacy is in favor of CDK4/6 inhibitors, and safety profiles are comparable between CDK4/6 inhibitors or PI3K/AKT/mTOR inhibitors plus endocrine therapy.



中文翻译:

CDK4/6 和 PI3K/AKT/mTOR 抑制剂在激素受体阳性、HER2 阴性转移性乳腺癌女性中的疗效和安全性比较:系统评价和网络荟萃分析。

背景

CDK4/6 抑制剂和 PI3K/AKT/mTOR 抑制剂都是激素受体 (HR) 阳性和人表皮生长因子受体 2 (HER2) 阴性转移性乳腺癌的新兴药物。目前,头对头比较试验的比较证据不足。该荟萃分析评估了这两组药物对 HR+/HER2- 转移性乳腺癌的疗效和安全性的比较。

方法

在 2010 年 1 月至 2019 年 12 月期间对 PubMed、Embase、CENTRAL、SciSearch 进行了系统搜索。采用了评估 CDK4/6 抑制剂或 PI3K/AKT/mTOR 抑制剂加内分泌治疗的临床益处和毒性的随机对照试验 (RCT)。主要终点是无进展生存期(PFS)和总生存期(OS)。次要终点是治疗相关的不良事件(TRAE)。合并风险比 (HR) 和风险率 (RR) 用于评估 CDK4/6 和 PI3K/AKT/mTOR 抑制剂之间的差异。

结果

本研究共确定了 20 项 RCT,包括 9771 名参与者。汇总结果显示,靶向治疗加内分泌治疗可显着延长 PFS。CDK4/6 抑制剂组的 PFS 相对优于 PI3K 抑制剂组(HR,1.43;95%CrI,1.12-1.61)。在平衡治疗线或转移部位后的结果中也证明了类似的结果,包括内脏和仅骨。合并结果显示,CDK4/6 抑制剂加内分泌治疗可以比 PI3K/mTOR 抑制剂显着改善 OS(HR,0.78;95%CrI,0.65-0.94)。CDK4/6 抑制剂和 PI3K/AKT/mTOR 抑制剂之间腹泻和皮疹的安全性特征一致,估计 RR 没有差异。几个 TRAE 表示特异性,例如,

结论

临床疗效有利于 CDK4/6 抑制剂,CDK4/6 抑制剂或 PI3K/AKT/mTOR 抑制剂加内分泌治疗的安全性相当。

更新日期:2020-05-12
down
wechat
bug