AUTHOR=Zhang Zhihao , Zhao Xin , Chen Jie TITLE=Adjuvant and neoadjuvant therapy with or without CDK4/6 inhibitors in HR+/HER2- early breast cancer: a systematic review and meta-analysis JOURNAL=Frontiers in Pharmacology VOLUME=Volume 15 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1438288 DOI=10.3389/fphar.2024.1438288 ISSN=1663-9812 ABSTRACT=Background

The combination of cyclin-dependent kinases 4/6 (CDK4/6) inhibitors and endocrine therapy is the standard treatment for patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced breast cancer. However, the role of CDK4/6 inhibitors in early breast cancer remains controversial.

Methods

This study aimed to evaluate the efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy versus endocrine therapy alone in patients with HR+, HER2- early breast cancer. A systematic review of Cochrane, PubMed and EMBASE databases was conducted. The efficacy endpoints of adjuvant therapy were invasive disease-free survival (IDFS), overall survival (OS) and distant relapse-free survival (DRFS). The efficacy endpoint included complete cell cycle arrest (CCCA) and complete pathologic response (PCR) with neoadjuvant therapy. Grade 3/4 adverse events (AEs) were assessed as safety outcomes.

Results

Eight randomized controlled trials (RCTs) were included in the study. CDK4/6 inhibitors combined with endocrine therapy showed a significant improvement in IDFS (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.68–0.97, P = 0.024), but not DRFS (HR = 0.84, 95% CI = 0.56–1.29, P = 0.106) or OS (HR = 0.96, 95% CI = 0.77–1.19, P = 0.692) in adjuvant therapy. In the neoadjuvant therapy setting, CDK4/6 inhibitors improved CCCA compared with the control group (RR = 2.08, 95% CI = 1.33–3.26, P = 0.001). The risk of 3/4 grade AEs increased significantly with the addition of CDK4/6 inhibitors to endocrine therapy.

Conclusion

The addition of CDK4/6 inhibitors in HR+/HER2- early breast cancer patients significantly improved IDFS in adjuvant therapy and CCCA in neoadjuvant. However, CDK4/6 inhibitors also showed significant toxicities during therapy.

Systematic Review Registration:

Identifier CRD42024530704.