Abstract PS2-04-12: Real-world overall survival with palbociclib plus an aromatase inhibitor (AI) in patients with HR+/HER2− metastatic breast cancer (MBC) who are overweight/obese

Abstract Background: A cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) has been the standard of care (SOC) as first-line (1L) treatment for hormone receptor-positive/HER2-negative (HR+/HER2−) MBC for the past decade. Palbociclib (PAL), the first CDK4/6i approved, received accelerated US approval in 2015 for HR+/HER2− MBC based on its demonstrated efficacy and safety profile. An increasing number of real-world (RW) studies have shown that 1L PAL+ET significantly improves progression-free survival, tumor response, and overall survival (OS) compared with ET alone across diverse HR+/HER2− MBC populations. Overweight and obesity are common conditions associated with an increased risk of breast cancer and can influence cancer treatment outcomes. However, little is known about the effectiveness of CDK4/6i+ET, specifically in patients (pts) with HR+/HER2− MBC who are overweight/obese in routine US clinical practice. Methods: This was a retrospective analysis of deidentified longitudinal data from the Flatiron Health Research Database. Pts were included if they were overweight or obese (BMI ≥25 kg/m2), had HR+/HER2− MBC, and initiated 1L PAL+AI or AI between Feb 2015−Jul 2024. OS was defined as the number of months from start of PAL+AI or AI alone to death. Date of death was a consensus mortality endpoint based on electric health records, Social Security Death Index, and obituary data, validated against the National Death Index. Pts were retrospectively followed until death, last medical activity, or January 2025 (data cut-off), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance pt characteristics. Cox proportional hazards models were used to estimate the relative effectiveness of PAL+AI vs AI alone. Results: A total of 8076 pts were eligible for analysis, including 5009 (62.0%) treated with PAL+AI and 3067 (38.0%) treated with AI alone. Compared with AI-alone pts, those treated with PAL+AI were younger and more likely to have ≥2 metastatic sites and lung/liver involvement but less likely to have ECOG score ≥2. After sIPTW, pt characteristics were generally balanced. Unadjusted median OS (95% confidence interval [CI]) was 51.4 (49.3-53.4) months with PAL+AI and 41.1 (38.9-43.3) months with AI (hazard ratio [HR]= 0.75 (0.71-0.80), P<0.0001). After sIPTW, median OS (95% CI) was 50.7 (48.7-53.1) months with PAL+AI and 42.4 (39.8-44.7) months with AI (HR=0.79 [0.74-0.85], P<0.0001). Consistent results were observed with 1:1 propensity score matching as a sensitivity analysis. See Table for baseline pt characteristics and OS results. Conclusions: Compared with AI alone, PAL+AI is associated with improved OS in pts with HR+/HER2- MBC who are overweight/obese in US real-world setting, supporting 1L PAL+AI as a SOC for pts with HR+/HER2- MBC who are overweight/obese. Citation Format: A. Brufsky, N. Iyengar, X. Liu, B. Li, D. Makari, L. McRoy, A. Cohen, M. Estevez, V. Abramson, R. Layman, G. Curigliano. Real-world overall survival with palbociclib plus an aromatase inhibitor (AI) in patients with HR+/HER2− metastatic breast cancer (MBC) who are overweight/obese [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-04-12.