Abstract PS5-02-03: Clinical Outcomes of Trastuzumab Emtansine (T-DM1) Following Trastuzumab Deruxtecan (T-DXd) in Metastatic Breast Cancer: A Single-Center Experience

Abstract Background: HER2-positive metastatic breast cancer (MBC) remains an oncological challenge afterdisease progression to pertuzumab-trastuzumab, and fam-trastuzumab deruxtecan. Data on treatmentoutcomes with T-DM1 following progression on trastuzumab deruxtecan (T-DXd) remain limited. This study evaluates the clinical outcomes of patients with HER2-positive MBC who received T-DM1 post-T-DXd. Methods: Demographics and clinical characteristics were summarized for the whole cohort who received T-DM1 after T-DXd. Continuous variables were summarized using medians and ranges, while categorical variables were summarized using frequencies and percentages. Overall survival (OS), defined as the time from the date of receiving T-DM1 to the date of death or last follow-up, progression-free survival (PFS),defined as the time from the date of receiving T-DM1 to the date of first documented disease progression or death, whichever occurred first, and time to progression (TTP), defined as the time from the date of receiving T-DM1 to the date of disease progression, were evaluated using the Kaplan-Meier method, and differences in survival curves were compared using the log-rank test. Cox proportional hazards regression models assessed associations between survival outcomes and clinical variables. The overall response rate was calculated based on the proportion of patients experiencing progressive or stable disease. A p-value 0.05 was considered significant. Analyses were performed using R version 4.2.2. Results: All 22 patients were female with a median age of 55.5 years. Median OS was 13.54 months (95% CI:8.74-NE), median PFS was 2.14 months (95% CI: 1.35-2.69), and median TTP was 2.20 months (95% CI: 1.38-2.69). HER2-low expression was associated with shorter OS (HR: 3.05), PFS (HR:4.30), and TTP (HR: 5.30). Overall response rate was 91%, with 68% showing progressive disease and 23% stable disease. No significant associations were identified between best response and other clinical variables. Conclusions: This study provides real-world evidence of the limited clinical efficacy of T-DM1 following resistant to T-DXd in HER2-positive MBC. Further research is warranted to develop novel therapeutic agents in this subgroup of patients and also to develop strategies to avoid resistant to T-DXd. Citation Format: V. Valero, Z. WANG, R. BASSETT, R. K. MURTHY, P. POHLMANN, D. TRIPATHY, A. RAGHAVENDRA. Clinical Outcomes of Trastuzumab Emtansine (T-DM1) Following Trastuzumab Deruxtecan (T-DXd) in Metastatic Breast Cancer: A Single-Center Experience abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-02-03.