Scholarlink

Background <p>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard of care for hormone receptor (HR)-positive, HER2-negative advanced/metastatic breast cancer (BC). However, the optimal strategy after progression remains uncertain.</p> Methods <p>PubMed, Cochrane, and Embase databases were searched in April 2025 for phase II/III clinical trials evaluating CDK4/6i rechallenge in advanced breast cancer. We evaluated progression-free survival (PFS) and overall survival (OS) using Cox proportional hazards models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were conducted on R (v.4.2.2).</p> Results <p>Eight trials including 1396 patients were included, of whom 839 received CDK4/6i rechallenge plus ET, and 557 received ET alone. Median PFS was 5.8&#xa0;months vs 3.7&#xa0;months, with a 29% reduction in risk of progression or death (HR 0.71; 95% CI 0.63–0.81; <i>P</i> &lt; 0.001). No OS benefit was observed (HR 1.04; 95% CI 0.70–1.55). Switching to a different CDK4/6i appears to confer greater benefit (HR 0.61; 95% CI 0.52–0.72), yet most patients who switched CDK4/6i received abemaciclib, which was associated with the longest PFS (7.9&#xa0;months) compared with palbociclib (4.6&#xa0;months) or ribociclib (5.5&#xa0;months). Patients harboring ESR1 or PIK3CA alterations demonstrated a median PFS of 5.3 (3.6–7.4) and 4.7 (3.6–6.7) months, respectively.</p> Conclusions <p>This meta-analysis suggests that CDK4/6 inhibitor rechallenge post-progression offers additional benefit to ET alone.</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

CDK4/6 inhibitors rechallenge post-progression in HR-positive HER2-negative advanced/metastatic breast cancer patients: a meta-analysis of Kaplan–Meier-reconstructed individual-level data

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月27日

查看全文
  • Jasmina Veta Darkovski,
  • Isabella Michelon,
  • Gabriela Gazzoni,
  • Isadora Mamede,
  • Yujin Jeong,
  • Ludimila Cavalcante

摘要

Background

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard of care for hormone receptor (HR)-positive, HER2-negative advanced/metastatic breast cancer (BC). However, the optimal strategy after progression remains uncertain.

Methods

PubMed, Cochrane, and Embase databases were searched in April 2025 for phase II/III clinical trials evaluating CDK4/6i rechallenge in advanced breast cancer. We evaluated progression-free survival (PFS) and overall survival (OS) using Cox proportional hazards models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were conducted on R (v.4.2.2).

Results

Eight trials including 1396 patients were included, of whom 839 received CDK4/6i rechallenge plus ET, and 557 received ET alone. Median PFS was 5.8 months vs 3.7 months, with a 29% reduction in risk of progression or death (HR 0.71; 95% CI 0.63–0.81; P < 0.001). No OS benefit was observed (HR 1.04; 95% CI 0.70–1.55). Switching to a different CDK4/6i appears to confer greater benefit (HR 0.61; 95% CI 0.52–0.72), yet most patients who switched CDK4/6i received abemaciclib, which was associated with the longest PFS (7.9 months) compared with palbociclib (4.6 months) or ribociclib (5.5 months). Patients harboring ESR1 or PIK3CA alterations demonstrated a median PFS of 5.3 (3.6–7.4) and 4.7 (3.6–6.7) months, respectively.

Conclusions

This meta-analysis suggests that CDK4/6 inhibitor rechallenge post-progression offers additional benefit to ET alone.