Comparative efficacy of Palbociclib and Everolimus with aromatase inhibitors in second line treatment of HR and HER2 negative metastatic breast cancer

Abstract

Background: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC) often develops resistance to endocrine therapy (ET), necessitating targeted therapies like Palbociclib (CDK4/6 inhibitor) and Everolimus (mTOR inhibitor). This retrospective cohort study compares their efficacy as second-line therapy combined with aromatase inhibitors in HR+/HER2 − MBC. Methods: In this retrospective observational cohort study, A cohort of 100 women with HR+/HER2 − MBC was analyzed, with 50 receiving Palbociclib plus an aromatase inhibitor and 50 receiving Everolimus plus an aromatase inhibitor. Propensity score matching balanced baseline characteristics (age, metastatic sites, prior treatments). The primary endpoint, progression-free survival (PFS), and secondary endpoint, overall survival (OS), were assessed using Kaplan-Meier analysis and Cox proportional hazards models. Adverse events were compared using Fisher’s exact test. Results: Median PFS was 19 months (95 CI: 16.2–21.8) for Palbociclib versus 11 months (95 CI: 8.7–13.3) for Everolimus (HR: 0.52, 95 CI: 0.32–0.85, P = 0.009). Median OS was 32 months (95 CI: 28.5–35.5) for Palbociclib versus 26 months (95 CI: 22.3–29.7) for Everolimus (HR: 0.68, 95 CI: 0.47–0.99, P = 0.045). Subgroup analyses showed stronger Palbociclib benefits in postmenopausal patients (PFS HR: 0.50, P = 0.008) and those with bone-only metastases (PFS HR: 0.48, P = 0.007). Adverse events included neutropenia (Palbociclib, 70) and mouth sores (Everolimus, 76), with comparable severe event rates (P = 0.298). Conclusion: Our study suggests that Palbociclib is associated with improved PFS and OS compared to Everolimus in second-line HR+/HER2 − MBC, particularly in postmenopausal and bone-only metastasis subgroups, with manageable toxicity. These findings support Palbociclib’s role in optimizing treatment. © The Author(s) 2025.