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

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.