Abstract PS5-02-08: Impact of Prior T-DM1 Exposure on the Efficacy of Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer

Abstract Introduction: Trastuzumab deruxtecan (T-DXd) has emerged as a highly effective antibody-drug conjugate for patients with HER2-positive metastatic breast cancer, particularly following progression on prior HER2-directed therapies. However, the clinical relevance of prior exposure to another HER2-targeted ADC, trastuzumab emtansine (T-DM1), on the efficacy of subsequent T-DXd remains unclear. Clarifying this sequencing effect is essential for optimizing treatment strategies in the advanced disease setting. Methods: This multicenter, retrospective cohort study evaluated patients with HER2-positive metastatic breast cancer who received T-DXd therapy. The primary objective was to assess the impact of prior exposure to another antibody-drug conjugate, T-DM1, on progression-free survival (PFS) following T-DXd treatment. Eligible patients were identified from institutional records across 21 oncology centers in Turkey, and clinical, pathological, and treatment data were collected. PFS was defined as the time from initiation of T-DXd to radiologic or clinical disease progression or last follow-up. Cox proportional hazards regression was used to estimate hazard ratios for progression. Results: A total of 199 patients were included, with a mean age of 45.8 ± 12.0 years (range: 21-83). T-DXd was administered at a median line of 3 (range: 1st-9th line). The majority of patients received T-DXd as a third (29.2%) or fourth-line therapy (25.6%). The median follow-up was 8.3 months, and the mean follow-up was 10.5 months (95% CI: approximately 9.5-11.5). Comorbidities were present in 31.2% of patients, and 57.3% were premenopausal. ER and PR positivity rates were 65.3% and 47.7%, respectively. HER2 status was IHC 3+ in 75.9% and IHC 2+/ISH+ in 24.1%. Prior to T-DXd, 67.3% of patients received T-DM1. Disease progression after T-DXd occurred more frequently in patients previously treated with T-DM1 (47.0% vs. 13.8%, p