Outcomes with Trastuzumab Deruxtecan (T-Dxd) by HER2 Status and Line of Treatment in a Large Real-World Database of Patients with Metastatic Breast Cancer.

1077 Background: In the clinical trial setting, T-DXd improves survival for patients with HER2+ and HER2-low metastatic breast cancer (MBC), and has also shown preliminary activity in HER2-0 MBC. Little real-world evidence is available on the performance of T-DXd. Methods: We conducted a retrospective observational study using the nationwide Flatiron Health electronic health record (EHR)-derived deidentified database to evaluate the real-world activity of T-DXd. We included patients with MBC who initiated T-DXd between 12/2019 and 1/2023. Tumors were categorized as HER2+ if positive at any timepoint, with HER2- cases further divided into HER2-low (IHC 1+ or 2+ not amplified) and HER2-0 (IHC 0) according to the last biopsy before T-DXd. Real world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 930 patients were included: 636 with HER2+, 268 with HER2-low and 26 with HER2-0 MBC. Among HER2- patients, 241 (82.0%) were HR+ and 53 (18.0%) were HR- (i.e., triple-negative). A total of 572 (61.5%) patients were White, 101 (10.9%) Black/African American, 88 (9.4%) Hispanic/Latino, 37 (4.0%) Asian and 132 (14.2%) other or missing. Median age was 59 [range 25, 84] and patients received T-DXd in the following lines of therapy (LOT): 54 (5.8%) as 1st line, 110 (11.8%) as 2nd line, 179 (19.2%) as 3rd line, 182 (19.6%) as 4th line and 405 (43.6%) as ≥5th line. Median number of LOT for advanced disease prior to T-DXd were 3 and 4, respectively, for HER2+ and HER2- patients. In patients with HER2+ MBC, rwPFS and OS were 12.1 and 26 months after initiating T-DXd, respectively. The longest rwPFS, 14.9 months, was observed in the 1st or 2nd LOT, followed by 14.1 months in LOT 3, 12.4 months in LOT 4, and 10.8 months in LOT ≥5. In patients with HER2- MBC, median rwPFS and OS were 6.3 and 15.5 months, respectively. The longest median rwPFS of 8.1 months was observed in the 1st or 2nd LOTs, followed by 6.9 months in LOT 4, 6.2 months in LOTs ≥5, and 6.0 months in LOT 3. Outcomes with T-DXd by HER2 and HR status are provided (Table). Updated data with a larger sample size will be presented. Conclusions: In the largest dataset to date, T-DXd showed favorable real-world activity for treating MBC, although rwPFS appeared shorter than what observed in clinical trials. Encouraging rwPFS was observed in understudied groups, such as patients with triple-negative and HR+/HER2-0 MBC. [Table: see text]