Abstract PS1-10-23: Real-world analysis of unmet need among patients in the US with HR+/HER2- mBC following endocrine therapy

Abstract Background: Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (immunohistochemistry 0, 1+, or 2+/in situ hybridization-negative) metastatic breast cancer (HR+/HER2- mBC) are treated with endocrine therapy (ET) ± CDK4/6 inhibitor as the preferred option in the first-line setting followed by ET ± targeted therapy. Most HR+ disease will eventually become ET resistant, at which point treatment is primarily limited to cytotoxic therapy. This study describes characteristics, treatment patterns, and real-world outcomes among patients with HR+/HER2- mBC in the post ET-based treatment setting. Methods: This retrospective, observational cohort study utilized electronic health record-derived de-identified data from the US nationwide Flatiron Health Research Database. Women aged ≥ 18 years with HR+/HER2- mBC who received post ET-based treatment from January 1, 2015, to December 31, 2024 were included. Patient characteristics, treatment patterns, time to next treatment or death (TTNTD), and real-world overall survival (rwOS) were described; rwOS was assessed by Kaplan-Meier methods. Results: 5012 patients were included, with a median age of 63 years at mBC diagnosis. Most were Caucasian (62%), treated in the community setting (82%), had ECOG PS 0-1 (78%) at start of first post ET-based treatment, were diagnosed with recurrent mBC (68%), and had ≥ 2 prior lines of ET-based treatment in the mBC setting (65%) The median time from mBC diagnosis to first post ET-based treatment was 19 months. The median follow-up after the first post ET-based treatment in the mBC setting was 12 months. Ninety-six percent of patients received chemotherapy-based regimens as their first post ET-based treatment; capecitabine monotherapy was the most prescribed chemotherapy (34%) followed by taxane monotherapy (18%). Thirty percent of patients who initiated a post ET-based treatment did not survive to the next line of treatment. The median (95% CI) rwOS from start of first post ET-based treatment was 13.4 (12.9-13.9) months. There was a decrease in median (95% CI) rwOS with each subsequent line of treatment, ranging from 10.7 (10.2-11.1) months (second post ET-based treatment) to 7.4 (6.4-8.6) months (fifth post ET-based treatment) (Table). Similar trends were observed for TTNTD. Conclusions: These findings establish the high unmet need in patients with HR+/HER2- mBC treated with the standard of care regimens following ET-based treatment. For these patients, options are limited primarily to chemotherapy, with almost one-third not surviving to receive the second line of post ET-based treatment. This highlights the importance of making the most robust agents available for this patient population and demonstrates a clear and urgent need for new effective treatments in this setting. Citation Format: J. O'Shaughnessy, M. Rehnquist, N. Sadetsky, W. Verret, P. Cinar, N. Sjekloca, L. Nguyen, R. Nanda, P. Sharma. Real-world analysis of unmet need among patients in the US with HR+/HER2- mBC following endocrine therapy [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 PS1-10-23.