SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1564437
This article is part of the Research TopicEvidence-Based Research and Clinical Application of Adverse Reactions and Management Strategies for Cancer Treatment DrugsView all 7 articles
Long-term Efficacy of CDK4/6 Inhibitors in Early HR+, HER2-High-Risk Breast Cancer: An Updated Systematic Review and Meta-Analysis
Provisionally accepted
- 1Department of Breast Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Background: The confirmed efficacy of combining CDK4/6 inhibitors with endocrine therapy (ET) in HR+, HER2− early breast cancer patients in longer follow-up necessitates further investigation. This meta-analysis aims to comprehensively assess the impact of follow-up duration on the therapeutic activity in high-risk patients.Methods: We systematically searched PubMed, Cochrane Library, Embase, Medline, Web of Science, and relevant conference abstracts up to October 19, 2024. The included RCTs examined CDK4/6 inhibitors with ET in HR+ HER2− early breast cancer patients. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated to analyze invasive disease-free survival (iDFS).Results: Four RCTs with 3-year and 4-year iDFS data (n=17,749) were included. The results showed that the CDK4/6 inhibitor group had significantly better iDFS compared to the ET group at both 3 years (HR = 0.81, 95% CI 0.70–0.94, P = 0.006) and 4 years (HR = 0.78, 95% CI 0.66–0.94, P = 0.007). Subgroup analysis revealed that in LN+ patients, the CDK4/6 inhibitor group also had significantly better iDFS at both 3 years (HR = 0.84, 95% CI 0.73–0.97, P = 0.02) and 4 years (HR = 0.74, 95% CI 0.68–0.81, P < 0.00001). For N0 patients, iDFS benefits became more evident over time. At 4 years, combination therapy showed significant improvement (HR = 0.65, 95% CI 0.45–0.94, P = 0.02). For stage II patients, CDK4/6 inhibitors combined with ET showed no statistically significant difference in iDFS at treatment completion (HR = 0.78, 95% CI 0.59–1.05, P = 0.10), but significantly improved iDFS at 4 years (HR = 0.66, 95% CI 0.50–0.87, P = 0.003).Conclusions: The iDFS improvement with CDK4/6 inhibitors becomes more evident over time, suggesting broader benefits and enhanced long-term efficacy for HR+, HER2- breast cancer patients especially with N0 or Stage II.
Keywords: CDK4/6 inhibitor, Early breast cancer, Meta-analysis, Follow-up duration, iDFS
Received: 21 Jan 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Liu, Su, Wu and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenjie Lv, Department of Breast Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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