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SYSTEMATIC REVIEW article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1438288

Adjuvant and neoadjuvant therapy with or without CDK4/6 inhibitors in HR+/HER2-early breast cancer: a systematic review and meta-analysis

Provisionally accepted
Zhihao Zhang Zhihao Zhang Xin Zhao Xin Zhao Jie Chen Jie Chen *
  • West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    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.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.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.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.

    Keywords: CDK4/6 inhibitors, HR-positive, adjuvant, breast cancer, Endocrine therapy

    Received: 21 Jun 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Zhang, Zhao and Chen. 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: Jie Chen, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.