Abstract PO1-17-05: Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in metastatic breast cancer patients with cardiovascular diseases
Authors: Brufsky Adam , Liu Xianchen , Li Benjamin , McRoy Lynn , Chen Connie , Makari Doris , Layman Rachel , Rugo Hope 
Published: May 2024

Abstract
Background Breast cancer survivors are at risk for mortality from cardiovascular diseases (CVD). CVD and their treatments can impact breast cancer treatment selection and clinical outcomes. A cyclin dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) is more effective than ET alone for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2) metastatic breast cancer (MBC). CDK4/6i plus ET is now the standard of care in the first-line setting for HR+/HER2 MBC. However, data on the effectiveness of CDK4/6i in MBC patients with CVD are limited. We compared overall survival (OS) and real-world progression-free survival (rwPFS) of palbociclib plus AI (PAL+AI) vs AI alone in HR+/HER2 MBC patients with CVD in routine US clinical practices. Methods The Flatiron Health longitudinal database contains electronic health records from &gt;280 cancer clinics, representing &gt;3 million actively treated cancer patients in the US. Using the Flatiron database, we conducted a retrospective analysis of 469 patients with HR+/HER2 MBC and CVD who started PAL+AI or AI as first-line therapy between February 2015 and March 2020. CVD prior to the initiation of PAL+AI or AI were identified based on their definitions within the National Cancer Institute-Comorbidity Index (NCI-CI), including myocardial infarction, congestive heart failure, peripheral vascular diseases, and cerebrovascular diseases. Patients were assessed from start of PAL+AI or AI to September 30, 2020 (data cutoff date), death, or last visit, whichever came first. OS was defined as months from start of PAL+AI or AI to death. rwPFS was defined as months from start of PAL+AI or AI to death or disease progression, evaluated based on clinical assessment or radiographic scan/tissue biopsy. Stabilized inverse probability treatment weighting (sIPTW) as primary analysis was used to balance baseline demographics and clinical characteristics. Cox proportional-hazards models were used to estimate the relative effectiveness of PAL+AI vs AI alone. Results Of the 469 eligible patients, 160 (34.1%) were treated with PAL+AI and 309 (65.9%) were treated with AI alone. Compared with AI-alone patients, those treated with PAL+AI were younger and were more likely to have de novo MBC, ≥2 metastatic sites, and lung/liver involvement. After sIPTW, patient characteristics were generally balanced. After sIPTW, median OS (95% confidence interval [CI]) was 40.7 months (30.956.0) in PAL+AI patients and 26.5 months (23.337.3) in AI patients (hazard ratio [HR]=0.732, 95% CI=0.5370.997, p=0.0476). Median rwPFS (95% CI) was 20.0 months (11.7–27.5) in PAL+AI patients and 12.5 months (9.718.3) in AI patients (HR=0.679, 95% CI=0.5120.900, p=0.0070). Consistent results were observed with multivariate Cox proportional-hazards models as sensitivity analysis. See Table for baseline patient characteristics and outcome results. Conclusions First-line PAL in combination with AI is associated with prolonged OS and rwPFS in patients with HR+/HER2 MBC and CVD in a real-world setting compared with AI alone. Further studies with larger cohorts and comprehensive assessments of comorbidities are needed to provide additional evidence of outcomes and safety of CDK4/6i plus AI for MBC patients with various comorbid conditions in routine clinical practice.

Citation Format: Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Doris Makari, Rachel Layman, Hope Rugo. Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in metastatic breast cancer patients with cardiovascular diseases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-05.