The effect of dose reduction of CDK4/6 inhibitors on survival in postmenopausal HR+ HER2-negative metastatic breast cancer


Ceylan F., Efil S. C., Şener Dede D., Tenekeci A. K., Bilgin B., Yücel Ş., ...More

Expert Review of Anticancer Therapy, vol.25, no.5, pp.579-588, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 5
  • Publication Date: 2025
  • Doi Number: 10.1080/14737140.2025.2490289
  • Journal Name: Expert Review of Anticancer Therapy
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.579-588
  • Keywords: CDK4/6 inhibitors, dose reduction, metastatic breast cancer, overall survival, progression-free survival, toxicity management
  • Ankara Yıldırım Beyazıt University Affiliated: Yes

Abstract

Background: This study aimed to evaluate the effect of dose reduction of CDK4/6 inhibitors on survival outcomes in postmenopausal patients with HR+HER2-negative metastatic breast cancer (mBC). Methods: A retrospective cohort study was conducted involving 164 postmenopausal patients with HR+ HER2-negative mBC who received CDK4/6 inhibitors between 2021 and 2024. Clinical parameters were systematically analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated based on dose reduction status. Survival outcomes were estimated using the Kaplan-Meier method, and independent prognostic factors were identified through multivariate Cox regression analysis. Results: The median age was 61 years, with a median follow-up of 23.5 months. The median PFS was 23.3 months, while median OS was not reached. Dose reduction occurred in 45 patients (27%), who exhibited significantly worse survival (PFS HR: 1.67, 95% CI: 1.02–2.72, p = 0.042; OS HR: 2.54, 95% CI:1.34–4.83, p = 0.004). Dose reduction and liver metastases were independent risk factors for shorter PFS and OS, while treatment in later lines was associated with shorter PFS. Conclusion: Dose reductions in CDK4/6 inhibitors were associated with worse survival outcomes in postmenopausal HR+ HER2− mBC patients. Future biomarker-driven studies are needed to guide personalized dose adjustments and optimize treatment efficacy.