Real-world outcomes of trastuzumab deruxtecan in HR-negative HER2-low metastatic breast cancer

This real-world, multicenter study evaluated trastuzumab deruxtecan (T-DXd) in 64 patients with HR-negative, HER2-low metastatic breast cancer between May 2022 and May 2025. The median lines of therapy were 3 (range 1-7). The objective response rate (ORR) was 35.9%, and the disease control rate was 75%. Median real-world progression-free survival (rwPFS) and overall survival were 5.0 months and 14.9 months, respectively. Multivariate analysis identified brain metastases and prior Trop-2 ADC treatment as independent predictors of shorter rwPFS. The most common adverse events were nausea (71.9%), fatigue (39.1%), anorexia (31.3%), and neutropenia (31.3%). Grade 3/4 adverse events were primarily neutropenia (9.4%), thrombocytopenia (7.8%), and nausea (3.1%). Despite lower ORRs in patients with BRCA1 mutations or MYC amplifications, the differences were not statistically significant. This study confirms the clinical efficacy and manageable safety profile of T-DXd in this population, identifying high-risk subgroups and potential resistance biomarkers to inform treatment decisions.