Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis
BackgroundThe 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 activit...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1564437/full |
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| author | Ying Liu Jun Su Ping Wu Wenjie Lv |
| author_facet | Ying Liu Jun Su Ping Wu Wenjie Lv |
| author_sort | Ying Liu |
| collection | DOAJ |
| description | BackgroundThe 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.MethodsWe systematically searched PubMed, Cochrane Library, Embase, Medline, Web of Science, and relevant conference abstracts up to 19 October 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).ResultsFour 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).ConclusionThe 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.Systematic Review RegistrationPROSPERO database, CRD42024593864. |
| format | Article |
| id | doaj-art-bb46eb0ac38f4351b6cb0aa764005b6b |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-bb46eb0ac38f4351b6cb0aa764005b6b2025-08-20T03:50:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15644371564437Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysisYing Liu0Jun Su1Ping Wu2Wenjie Lv3Department of Breast Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Breast Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Breast Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackgroundThe 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.MethodsWe systematically searched PubMed, Cochrane Library, Embase, Medline, Web of Science, and relevant conference abstracts up to 19 October 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).ResultsFour 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).ConclusionThe 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.Systematic Review RegistrationPROSPERO database, CRD42024593864.https://www.frontiersin.org/articles/10.3389/fphar.2025.1564437/fullCDK4/6 inhibitorearly breast cancermeta-analysisfollow-up durationiDFS |
| spellingShingle | Ying Liu Jun Su Ping Wu Wenjie Lv Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis Frontiers in Pharmacology CDK4/6 inhibitor early breast cancer meta-analysis follow-up duration iDFS |
| title | Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis |
| title_full | Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis |
| title_fullStr | Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis |
| title_full_unstemmed | Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis |
| title_short | Long-term efficacy of CDK4/6 inhibitors in early HR+, HER2- high-risk breast cancer: An updated systematic review and meta-analysis |
| title_sort | long term efficacy of cdk4 6 inhibitors in early hr her2 high risk breast cancer an updated systematic review and meta analysis |
| topic | CDK4/6 inhibitor early breast cancer meta-analysis follow-up duration iDFS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1564437/full |
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