454P Real-world (RW) considerations in treatment (tx) choice post-endocrine therapy (ET) in patients (pts) with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC)

Background:In HR+/HER2-mBC after ET, tx choice for antibody-drug conjugates (ADCs) or chemotherapy (chemo) depends on factors such as demographics, disease characteristics, prior tx, and comorbidities.We present RW results of considerations for first-line (1L) post-ET tx choice.Second-line+ post-ET results are forthcoming. Methods: This was an observational retrospective cohort study of US pts in the Flatiron Health (FH) or PharMetrics Plus (PP) databases who received 1L post-ET tx with an approved ADC (trastuzumab deruxtecan [T-DXd]) or chemo.Diagnoses of mBC were from Jan 1 2015 to Jul 31 2025.The index period (first receipt of 1L post-ET tx) was Apr 27 2022 to Jul 31 2025 (FH) or Mar 31 2025 (PP).Multivariate logistic regression identified independent predictors of 1L post-ET tx with T-DXd vs chemo.Results: The analysis included 2960 pts (T-DXd n = 608 [21%], chemo n = 2352 [79%]) in FH and 1488 (T-DXd n = 153 [10%], chemo n = 1335 [90%]) in PP.After adjusting for covariates, FH pts with T-DXd tx (vs chemo) were more likely to have higher body mass index (BMI), more recent mBC diagnosis, higher number of prior lines of mBC ET, HER2 low disease, recurrent mBC, and more likely to be non-Hispanic (NH) Asian and live in the Midwest (Table ).PP pts with T-DXd tx were more likely to have liver and bone metastases and no smoking history.In both FH and PP, pts with T-DXd tx were more likely to have brain metastases and longer time from mBC diagnosis to 1L post-ET start.