Scholarlink

Purpose <p>Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus aromatase inhibitor (AI) is the recommended first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC). CDK4/6i head-to-head trials have not been conducted, and randomized controlled trials (RCTs) report inconsistent overall survival (OS) results despite similar effects on the primary endpoint of progression-free survival. Real-world evidence can complement RCTs but selection biases and confounders can challenge interpretation. Target trial emulation applies the principles of RCTs to observational data to overcome such challenges. We emulated a hypothetical target trial to investigate whether causal differences in OS between patients receiving first-line CDK4/6i plus AI exist in the real-world clinical setting.</p> Methods <p>We used de-identified data (Flatiron Health mBC Enhanced Data Mart) from patients ≥ 18 years old at primary diagnosis who were treated with first-line palbociclib/ribociclib/abemaciclib plus AI for mBC between 2018 and 2024. Statistical adjustments included stabilized inverse-probability weighting (sIPTW), investigation of missing data mechanisms, and analyses for unmeasured confounders.</p> Results <p>2626 patients were included (palbociclib n = 1686; ribociclib n = 537; abemaciclib n = 403). After sIPTW, baseline characteristics were balanced between groups and there was no observable difference in real-world OS (ribociclib vs palbociclib, adjusted hazard ratio 1.00, 95% CI: 0.81–1.24; abemaciclib v palbociclib: 0.91, 95% CI: 0.74–1.14). Results were consistent after sensitivity analyses.</p> Conclusion <p>Using target trial emulation, real-world OS is similar with palbociclib/ribociclib/abemaciclib plus AI. These findings may contribute to the development of combination strategies to improve clinical outcomes and to guide clinical decision-making.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Comparative effectiveness of CDK4/6 inhibitors in metastatic breast cancer: using the target trial emulation framework to investigate overall survival in routine care

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月7日

查看全文
  • Adam M. Brufsky,
  • Richard S. Finn,
  • Otto Metzger,
  • Rodrigo Goncalves,
  • Cynthia Huang-Bartlett,
  • Sameet Sreenivasan,
  • Ula Nur,
  • Jessica Davies,
  • Alex Grigorenko,
  • Gráinne H. Long

摘要

Purpose

Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus aromatase inhibitor (AI) is the recommended first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC). CDK4/6i head-to-head trials have not been conducted, and randomized controlled trials (RCTs) report inconsistent overall survival (OS) results despite similar effects on the primary endpoint of progression-free survival. Real-world evidence can complement RCTs but selection biases and confounders can challenge interpretation. Target trial emulation applies the principles of RCTs to observational data to overcome such challenges. We emulated a hypothetical target trial to investigate whether causal differences in OS between patients receiving first-line CDK4/6i plus AI exist in the real-world clinical setting.

Methods

We used de-identified data (Flatiron Health mBC Enhanced Data Mart) from patients ≥ 18 years old at primary diagnosis who were treated with first-line palbociclib/ribociclib/abemaciclib plus AI for mBC between 2018 and 2024. Statistical adjustments included stabilized inverse-probability weighting (sIPTW), investigation of missing data mechanisms, and analyses for unmeasured confounders.

Results

2626 patients were included (palbociclib n = 1686; ribociclib n = 537; abemaciclib n = 403). After sIPTW, baseline characteristics were balanced between groups and there was no observable difference in real-world OS (ribociclib vs palbociclib, adjusted hazard ratio 1.00, 95% CI: 0.81–1.24; abemaciclib v palbociclib: 0.91, 95% CI: 0.74–1.14). Results were consistent after sensitivity analyses.

Conclusion

Using target trial emulation, real-world OS is similar with palbociclib/ribociclib/abemaciclib plus AI. These findings may contribute to the development of combination strategies to improve clinical outcomes and to guide clinical decision-making.