Real-world (rw) study of the treatment journey following antibody-drug conjugate (ADC) initiation and overall survival (OS) in breast cancer (BC) in a US community setting.

e13089 Background: ADCs have transformed the BC treatment landscape by providing clinically meaningful improvements in patient (pt) outcomes. This observational study aimed to describe the pt population, treatment patterns, and outcomes among pts with BC who received ADC treatment in a rw setting. Methods: Based on de-identified, pt-level data in a US community setting from the iKnowMed EHR database (cut off: Feb 28, 2025), this study identified adult pts with BC who initiated a 1st ADC (index ADC) between Jan 2020 and Aug 2024. Real world overall survival (rwOS) from ADC initiation to death from any cause was assessed by BC subtypes and ADC settings. Results: Among 4924 pts with BC who received an ADC, 1880 had HR+/HER2+, 1057 had HR+/HER2−, 666 had HR−/HER2+, 674 had triple-negative breast cancer (TNBC), and 647 had unknown subtype. Pts were predominantly female (99.4%), median age was 60 y (range, 21–≥90), and median follow-up was 14.6 mo (range, 0.1–61.7). At initial diagnosis, 36.7% had stage IV disease. Among 687 pts (14.0%) who received a 2nd ADC, use of trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), and sacituzumab govitecan (SG) as the index ADC was 55, 39, and 34 pts in metastatic regimen 1 (R1); 58, 43, and 36 in R2; and 49, 41, and 30 in R3, respectively. Across metastatic settings, most pts received SG as 2nd ADC after T-DXd, and T-DXd as 2nd ADC after T-DM1 or SG. Among pts receiving ≥2 of any metastatic regimen, 12-mo rwOS ranged from 81.1–91.1% for HR+/HER2+, 79.7–83.3% for HR−/HER2+, 59.3–66.7% for HR+/HER2−, and 54.9–61.4% for TNBC. Median rwOS for pts who received ≥2 of any metastatic regimen was 32.2 mo to not reached for HR+/HER2+, 27.6–38.7 mo for HR−/HER2+, 17.2–18.4 mo for HR+/HER2−, and 12.6–15.4 mo for TNBC. Conclusions: Consistent with contemporary approvals, T-DM1 is largely used for HER2+ BC in the adjuvant setting. T-DXd use becomes more frequent and nearly equal to T-DM1 use for HER2+ BC in R1, but then dominates in R2+. T-DXd is dominant for HR+/HER2− BC across R1-R3+. Survival outcomes among pts receiving ≥2 metastatic regimens highlight meaningful differences by subtype and establish contemporary rwOS reference points for clinical practice and future real-world comparative effectiveness studies. Distribution of index ADC for BC by subtype. ADC Treatment HR+/HER2+ (n = 1880) HR+/HER2− (n = 1057) HR−/HER2+ (n = 666) TNBC (n = 674) T-DM1 T-DXd SG T-DM1 T-DXd SG T-DM1 T-DXd SG T-DM1 T-DXd SG Adjuvant n 1210 8 333 5 100% 100% 100% 100% R1 n 85 80 2 1 87 31 49 55 2 43 153 50.9% 47.9% 1.2% 0.8% 73.1% 26.1% 46.2% 51.9% 1.9% 21.9% 78.1% R2 n 79 89 1 2 108 47</jats:td