Abstract PS5-05-05: Correlating time to treatment discontinuation with overall survival: real-world data on outcomes for first-line endocrine therapy + CDK4/6 inhibitor in metastatic breast cancer

Abstract Background Endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is the standard-of-care first-line (1L) treatment for hormone receptor-positive (HR+)/HER2-negative (HER2−) metastatic breast cancer (mBC). Given that outcomes tend to worsen following progression to next-line therapy, understanding the relationship between the duration of 1L treatment and subsequent outcomes may be an important factor for clinical decision-making. This real-world, retrospective, observational cohort study investigated the relationship between time to discontinuation (TTD) of 1L therapy and overall survival (OS) in patients with HR+/HER2− mBC. Methods Adults with HR+/HER2− mBC were identified from electronic health records in the US Flatiron Health Database. Included patients had started 1L ET + CDK4/6i between March 1, 2018, and March 31, 2024, and had ≥2 clinical activities on different days after 1L initiation. Patients were followed until September 30, 2024. Descriptive statistics were used to summarize demographics, baseline characteristics, and treatment patterns. 1L TTD was defined as time from 1L initiation to final administration of 1L therapy (whichever component was administered last) or death. TTD and OS were assessed using Kaplan-Meier methodology. The relationship between 1L TTD and OS was assessed using rank correlation and a multivariate, covariate-adjusted, time-dependent Cox regression model. Results A total of 2910 patients were included, with a mean age of 63.2 years. Most were White (66.2%) and postmenopausal (71.4%), with Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1 (63.2%), and estrogen receptor (ER) expression >70% (82.0%); 49% had recurrent disease (4.7% unknown), and few had liver metastases (16.1%). With a median (interquartile range) follow-up of 24.8 (14.0-41.0) months, median 1L TTD was 20.6 (95% CI: 19.4-22.0) months, and median OS was not reached. OS rate was 92.1% at 12 months and 83.8% at 24 months. There was a strong positive correlation between TTD and OS (r = 0.74 [95% CI: 0.70-0.78]). For each additional month on 1L treatment, the adjusted hazard ratio for OS was 0.95 (95% CI: 0.94-0.96; p<0.001). In real-world terms, this means that an additional 2, 4, 6, 8, and 10 months on 1L treatment would result in cumulative hazard ratios (calculated as 0.95^number of months) of 0.90, 0.81, 0.74, 0.66, and 0.60, respectively, and a 10%, 19%, 26%, 34%, and 40% lower risk of death, respectively. Lower ECOG PS, de novo disease, and ER expression >70% were also associated with better survival outcomes. Age, region, menopausal status, and practice type were not associated with survival outcomes. Conclusions In this real-world dataset, a longer duration of 1L treatment prior to clinical progression was highly positively correlated with longer OS, suggesting a clinical benefit to extending 1L treatment in HR+/HER2− mBC. It is therefore critical to identify ways to increase the duration of 1L therapy to improve patient outcomes. Citation Format: E. Mayer, K. A. Betts, R. Ramasubramanian, X. Nie, T. Pham, C. Chen. Correlating time to treatment discontinuation with overall survival: real-world data on outcomes for first-line endocrine therapy + CDK4/6 inhibitor in metastatic breast cancer [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 PS5-05-05.