Outcomes of CDK4/6 Inhibitor-Based Therapy in Premenopausal HR+/HER2- Metastatic Breast Cancer: Real World Data From A Multicenter Study

Pharmacotherapy. 2026 Apr;46(4):e70134. doi: 10.1002/phar.70134.

Abstract

Background: Breast cancer is the leading cause of cancer-related death in women worldwide. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) represents the most common subtype. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET) constitute standard first-line treatment, yet evidence comparing ribociclib and palbociclib in peri-/premenopausal patients remains limited. This study aimed to evaluate and compare the real-world efficacy and safety profiles of ribociclib versus palbociclib in combination with ET in this patient population.

Methods: This multicenter, retrospective study included 267 peri-/premenopausal patients with HR+/HER2- MBC treated with palbociclib (n = 86) or ribociclib (n = 181) plus ET across five centers in Turkey between 2020 and 2024. Primary end points were progression-free survival (PFS) and overall survival (OS); secondary end points included objective response rate (ORR) and safety. Survival analyses used Kaplan-Meier and Cox regression methods using R software; adverse events were graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Results: The mean age was 42.96 years. Median follow-up was 19.6 months for palbociclib and 13.3 months for ribociclib (p = 0.003). No statistically significant differences were observed between palbociclib and ribociclib in median PFS (24.05 vs. 24.41 months; HR: 1.06; p = 0.94) or OS (not reached vs. 41.03 months; p = 0.86). The ORR was comparable at 64% for palbociclib and 69% for ribociclib (p = 0.459). Safety profiles were similar; any-grade adverse events occurred in 77.9% of palbociclib and 80.7% of ribociclib patients (p = 0.600). Neutropenia was the most common toxicity (72.1% palbociclib vs. 74.0% ribociclib). Grade 3-4 adverse events occurred in 29.1% of the palbociclib group and 40.3% of the ribociclib group (p = 0.074). Subgroup analyses showed consistent treatment effects across age, visceral involvement, and line of therapy.

Conclusion: In real-world peri-/premenopausal patients with HR+/HER2- MBC, ribociclib and palbociclib combined with ET demonstrate comparable efficacy and tolerability. These findings support flexible treatment choice based on individual patient profiles and preferences.

Keywords: CDK4/6 inhibitors; HR+/HER2− breast cancer; palbociclib; ribociclib.

Publication types

  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adult
  • Aminopyridines* / administration & dosage
  • Aminopyridines* / adverse effects
  • Aminopyridines* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cyclin-Dependent Kinase 4* / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6* / antagonists & inhibitors
  • Erb-b2 Receptor Tyrosine Kinases / metabolism
  • Female
  • Humans
  • Middle Aged
  • Piperazines* / administration & dosage
  • Piperazines* / adverse effects
  • Piperazines* / therapeutic use
  • Premenopause
  • Progression-Free Survival
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Purines* / administration & dosage
  • Purines* / adverse effects
  • Purines* / therapeutic use
  • Pyridines* / administration & dosage
  • Pyridines* / adverse effects
  • Pyridines* / therapeutic use
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Piperazines
  • palbociclib
  • ribociclib
  • Purines
  • Aminopyridines
  • Cyclin-Dependent Kinase 4
  • Erb-b2 Receptor Tyrosine Kinases
  • Pyridines
  • Cyclin-Dependent Kinase 6
  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • ERBB2 protein, human
  • CDK6 protein, human
  • Receptors, Progesterone
  • Receptors, Estrogen