Abstract PS5-04-07: Real world experience with trastuzumab deruxtecan for metastatic breast cancer at a major Australian cancer centre

Abstract BACKGROUND: Trastuzumab deruxtecan (T-DXd) is approved for HER2-low and HER2+ metastatic breast cancer (MBC), offering significant clinical benefit. However, treatment-related toxicities—particularly nausea, vomiting and weight loss—can substantially impair patient quality of life and lead to early discontinuation. We evaluated real world efficacy and tolerability of T-DXd in an Australian context. METHODS: We conducted a retrospective cohort study of patients aged ≥18 years with MBC treated with T-DXd between May 2019 and December 2024 at a single tertiary Australian cancer centre. Demographic, clinicopathologic, treatment and toxicity data were extracted from medical records. Kaplan-Meier analysis was utilized for progression-free survival (PFS), with censoring of patients still on treatment. Results: Data from 75 patients was analyzed with a median follow-up of 15.5 months (95% CI 16.3-23, range: 0.8-68.7). Median age was 46 years (IQR 39-56). 64% had recurrent metastatic disease; 36% were de novo metastatic. 36 patients (48%) were HER2-low and 39 patients (52%) were HER2+. Hormone receptor (HR) positivity was observed in 60% (36% HER2-low and 24% HER2+). 31% had liver metastases. Median PFS1 was 6.5 months (95% CI 5.8-10.3, range: 0.2-31) in the HER2-low cohort and 19.3 months (95% CI 15.6-23.6, range: 1.1-52.4) in the HER2+ cohort. Median PFS1 was higher in HR+ HER2-low (7.23 months, 95% CI 6-11.7, range: 1.3-31) compared to HR- HER2-low (5.5 months, 95% CI 2.5-8.6, range: 0.2-12.9). Number of prior lines of therapy was higher in HER2-low (median 2, range: 0-14) than HER2+ (median 1, range: 0-6). Common toxicities were nausea, vomiting and weight loss, at rates higher than reported in trial data (Table 1). Dose reductions (DRs) occurred in 33 patients (44%), with 6 (8%) receiving upfront DR for performance status and 27 (36%) requiring at least one subsequent DR, most often due to nausea/vomiting (21.3%). DR typically occurred after a median of 6 cycles (range: 1-40). Treatment discontinuation due to toxicity occurred in 7 patients (9.3%), most often due to interstitial lung disease (ILD; 5 patients, 6.7%). 1 patient (1.3%) discontinued due to hepatotoxicity resulting in thrombocytopenia and 1 patient (1.3%) due to fatigue. 48 patients (64%) had progressed on T-DXd. 32 patients (42.7%) received next line therapy, most commonly capecitabine in HER2-low (7 patients, 9.3%) and trastuzumab emtansine in HER2+ (4 patients, 5.3%). Median PFS2 was 3.4 months (95% CI 2.8-7, range: 0.7-20.5). CONCLUSION In this real world cohort, T-DXd demonstrated substantial activity in HER2-low and HER2+ MBC, consistent with trial data. However, treatment-related toxicities—especially nausea, vomiting, weight loss and ILD—often led to dose modifications and drove discontinuation in ∼10% of patients. Interventions targeting emesis and cachexia may help improve tolerability and duration of treatment. Citation Format: M. Li, C. T. Van Geelen, L. E. Lara Gonzalez, K. Clarke, S. Lingaratnam, P. A. Francis, S. Loi. Real world experience with trastuzumab deruxtecan for metastatic breast cancer at a major Australian cancer centre 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 PS5-04-07.