First-line endocrine-based therapy in metastatic breast cancer: Real-world evidence on patient characteristics, treatment patterns, and survival outcomes.

216 Background: Endocrine therapy (ET) remains the backbone of first-line (1L) treatment for hormone receptor-positive (HR+)/HER2-negative (HER2−) metastatic breast cancer (mBC). Predicting response to ET presents a major clinical challenge; understanding the underlying patient and disease heterogeneity is key. This retrospective, observational cohort study examined the real-world characteristics, biomarker profiles, treatment patterns, and survival outcomes of patients (pts) with HR+/HER2− mBC treated in the 1L setting. Methods: Adults with HR+/HER2− mBC who started 1L ET + CDK4/6 inhibitor (CDK4/6i) between March 1, 2018 and March 31, 2024 were identified from Flatiron Health Data and followed until September 30, 2024. Descriptive statistics were used to summarize demographics, baseline characteristics, genomic alterations, and treatment patterns. A multivariate logistic regression analysis was used to identify factors associated with progression ≤6 m on 1L ET for mBC. Real-world progression-free survival (rwPFS), time to chemotherapy (TTC), and overall survival (OS) were evaluated using the Kaplan-Meier method. Results: A total of 2910 pts were included, treated with CDK4/6i + either aromatase inhibitor (AI; 62.7%), fulvestrant (23.3%), or other ET (14.0%). Mean age was 63.2 years, 49.0% had de novo disease, 71.4% were post-menopausal, 9.3% had ER expression ≤70%, and 20.7% progressed ≤6 m. Factors associated with ≤6 m progression included younger age, worse ECOG PS, recurrent disease, postmenopausal status, and liver metastases. The subgroup of pts receiving CDK4/6i + AI (n = 1516) had similar baseline characteristics: mean age 63.1 years, 62.6% de novo disease, 71.7% post-menopausal, 8.2% with ER expression ≤70%, and 17.0% progressed ≤6 m. In the CDK4/6i + AI population, rates of rwPFS at 12 and 24 months were 71.0% and 51.6%, respectively. Pts with ≤6 m vs > 6 m progression had lower median TTC (25.1 months vs not reached [NR]; 28.3% vs 14.8% received 2L chemotherapy, Table) and had worse median OS (29.9 months vs NR). Conclusions: These data highlight the heterogeneous nature of HR+/ HER2− mBC. Poor response to 1L ET + CDK4/6i was common, and challenging as pts progressing ≤6 m experienced a shorter TTC and decreased OS. Subsequent therapy treatment patterns indicate an unmet need to extend the duration of 1L ET to improve pt outcomes. 2L treatment 3L treatment Subsequent therapy, n (%) ≤6 m (n=187) >6 m (n=641) ≤6 m (n=106) >6 m (n=340) Chemotherapy 53 (28.3) 95 (14.8) 61 (57.5) 138 (40.6) CDK4/6i + ET 64 (34.2) 298 (46.5) 11 (10.4) 46 (13.5) Targeted therapy + ET 38 (20.3) 95 (14.8) 18 (17.0) 85 (25.0) ET monotherapy 26 (13.9) 128 (20.0) 8 (7.5) 47 (13.8) Other 6 (3.2) 25 (3.9) 8 (7.6) 24 (7.0)