Abstract P4-12-04: Real-world effectiveness of palbociclib plus an aromatase inhibitor in HR+/HER2- MBC patients living in disadvantaged neighborhoods

Abstract Background: Palbociclib (PAL) in combination with endocrine therapy (ET) has been approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced/metastatic breast cancer (MBC) since February 2025. Despite extensive real-world data in a variety of populations, little is known about the use and effectiveness of PAL combination in MBC patients living in disadvantaged neighborhoods. The current study aimed to compare overall survival (OS) and real-world progression-free survival (rwPFS) of first-line PAL plus an aromatase inhibitor (AI) vs AI alone in HR+/HER2 MBC patients living in disadvantaged neighborhoods in the US. Methods: This is a retrospective observational study of HR+/HER2- MBC patients in the Flatiron Health longitudinal database. The database contains electronic health records from >280 cancer clinics, representing >3 million actively treated cancer patients in the US. Patients were included in this analysis if they had HR+/HER2- MBC, were ≥18 years, started PAL + AI as first-line therapy between February 2015 and June 2022 (index period), and lived in disadvantaged neighborhoods. Neighborhood disadvantage was measured with the Yost index, a composite measure of neighborhood social economic status. The Yost index score ranges from 1 (the first quintile) to 5 (the fifth quintile), with higher scores indicating higher socioeconomic status of the neighborhoods. Neighborhood disadvantage was defined as a Yost Index score of 1-2. Patients were retrospectively assessed from start of PAL+AI to December 2022 (data cutoff date), death, or last medical activity, whichever came first. OS was defined as months from start of PAL+AI to death. rwPFS was defined as months from start of PAL+AI to death or disease progression, evaluated based on clinical assessment or radiographic scan/biopsy. Stabilized inverse probability of treatment weight (sIPTW) was used to balance baseline demographics and clinical characteristics. 1:1 propensity score matching (PSM) was performed as sensitivity analysis. Results: Of the 723 patients who were eligible for the analysis, 394 and 329 patients received PAL+AI and AI, respectively. Median follow-up was 27.2 months for PAL+AI and 25.7 months for AI treated patients. Compared with AI group, PAL+AI group was younger (median age 66.0 vs 69.0 years) and had higher proportions of de novo MBC (39.9% vs 24.0%) and lung/liver metastases (32.0% vs 19.8%). After sIPTW, baseline demographic and clinical characteristics were generally well balanced between PAL+AI and AI groups. After sIPTW, median OS was 57.1 (95%CI=47.2-70.8) months in PAL+AI group vs 38.2 (95%CI=29.6-48.0) months in AI group (HR=0.70, 95%CI=0.55-0.90, p =0.0053). Median rwPFS was 19.1 (95%CI = 15.8 – 24.2) months in PAL+AI group and 14.0 (95%CI=10.7-19.7) months in AI group (HR=0.66, 95%CI=0.52-0.84, p =0.0007). Sensitivity analysis with 1:1 PSM showed consistent results. Conclusions: This real-world data analysis demonstrated that first-line palbociclib plus AI was associated with prolonged OS and rwPFS in HR+/HER2- MBC patients living in disadvantaged neighborhoods. These findings support use of first-line palbociclib in combination with endocrine therapy in this population. Citation Format: Filipa Lynce, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Raymond Liu, Hope S. Rugo. Real-world effectiveness of palbociclib plus an aromatase inhibitor in HR+/HER2- MBC patients living in disadvantaged neighborhoods [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-12-04.