Skip to main content

SYSTEMATIC REVIEW article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1369420

Confirming the Efficacy and Safety of CDK4/6 Inhibitors in the Firstline Treatment of HR+ Advanced Breast Cancer: A Systematic Review and Meta-Analysis

Provisionally accepted
Mengyuan Li Mengyuan Li Xin Guan Xin Guan Xinyue Ji Xinyue Ji Yufei Wang Yufei Wang Lei Tian Lei Tian *
  • School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China

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

    Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods. Methods: Phase II or III randomized controlled trials in treatment-naive HR+ patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes. Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (P = -1) and the first-order FP model (P = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR=9.84, 95%CI: 8.13-11.95), especially for palbociclib (OR=14.04, 95%CI: 10.52-18.90). Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR+ advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively.

    Keywords: CDK4/6 inhibitor, Hormone-receptor-positive, Advanced breast cancer, fractional polynomials models, Meta-analysis

    Received: 12 Jan 2024; Accepted: 22 Jul 2024.

    Copyright: © 2024 Li, Guan, Ji, Wang and Tian. 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: Lei Tian, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, 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.