ER+/HER2-转移性乳腺癌内分泌治疗联合靶向治疗方案的定量评估:基于模型的meta分析

Quantitative evaluation of combination of targeted therapy regimens and endocrine therapy for ER+/HER2-metastatic breast cancer:a model-based meta-analysis

目的定量比较CDK4/6抑制剂与PI3K/AKT/mTOR抑制剂治疗ER+/HER2-转移性乳腺癌的疗效和安全性。方法采用参数化生存函数模型分析总生存期(OS)和无进展生存期(PFS)的时间进程,在单臂meta分析中使用随机效应模型汇总任意级别和3~5级不良事件发生率。结果本研究纳入48篇文献,包括7881例患者。结果显示,CDK4/6抑制剂的中位OS为40.7个月,中位PFS为14.8个月;而PI3K/AKT/mTOR抑制剂的中位OS为29.8个月,中位PFS为8.3个月。此外,内脏转移患者的比例和联合使用的内分泌治疗药物类型显著影响疗效。在不良事件方面,CDK4/6抑制剂表现出相对较高的血液学不良事件发生率。结论CDK4/6抑制剂的疗效显著优于PI3K/AKT/mTOR抑制剂。本研究为CDK4/6抑制剂在ER+/HER2-转移性乳腺癌临床诊疗指南中的一线推荐使用提供了可靠的定量证据。

Objective To quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2-metastatic breast cancer.Methods A parametric survival function was used to analyze the temporal progression of overall survival(OS)and progression-free survival(PFS).The incidence of adverse events,both any grade and grade 3~5,was summarized with the random-effect model in a single-arm meta-analysis.Results This study included 48 publications,with a total of 7881 patients.CDK4/6 inhibitors had a median OS of 40.7 months,a median PFS of 14.8 months,contrasting with PI3K/AKT/mTOR inhibitors with a median OS of 29.8 months and a median PFS of 8.3 months.The proportion of patients with visceral metastases and specific combinations of endocrine therapies obviously impacted the treatment efficacy.In terms of safety profiles,CDK4/6 inhibitors were associated with a notably elevated incidence of hematological adverse events.Conclusion CDK4/6 inhibitors demonstrate a superior therapeutic advantage over PI3K/AKT/mTOR inhibitors.Our study furnishes robust quantitative evidence for the choice of combining CDK4/6 inhibitors with endocrine therapy for ER+/HER2-metastatic breast cancer in clinical guidelines.