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Efficacy and Safety of Datopotamab Deruxtecan From a Single‐Institution Experience in Hormone Receptor–Positive, HER2 ‐Negative Metastatic Breast Cancer After Multiple Prior Therapies Including Antibody–Drug Conjugates

Year: 2026

Type: article

Abstract: BACKGROUND: Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) with a topoisomerase I inhibitor payload and was approved by the Japan Pharmaceuticals and Medical Devices Agency in 2025 for patients with unresectable or recurrent hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer previously treated with chemotherapy. In the pivotal TROPION-Breast01 trial, most patients had received 1 or 2 prior systemic regimens. However, in routine clinical practice, Dato-DXd is often used in heavily pretreated patients, including those with prior ADC exposure. We evaluated the efficacy and safety of Dato-DXd in this population. METHODS: We retrospectively analyzed 18 patients with HR+/HER2- metastatic or recurrent breast cancer who received Dato-DXd at our institution between May and December 2025. Clinical data from electronic medical records were reviewed to assess treatment efficacy and treatment-related adverse events (TRAEs). RESULTS: All patients were female, with a median age of 56 years (range, 48-81). Patients were heavily pretreated, with a median of seven prior systemic treatment lines (range, 2-11); 72.2% had previously received trastuzumab deruxtecan (T-DXd). Median real-world progression-free survival (rwPFS) was 3.2 months. Patients with prior T-DXd exposure had significantly shorter rwPFS than T-DXd-naïve patients (2.8 vs. 6.4 months, p < 0.01). TRAEs were generally mild and manageable. The most common TRAEs included alopecia, fatigue, constipation, stomatitis, nausea, and elevated liver transaminases. Five patients required dose reductions, but no treatment discontinuations or fatal events occurred. No cases of interstitial lung disease occurred. CONCLUSIONS: In this cohort of heavily pretreated HR+/HER2- metastatic or recurrent breast cancer, Dato-DXd showed limited clinical activity compared with clinical trials, particularly among patients previously treated with T-DXd. Nevertheless, Dato-DXd was safely administered with toxicity management. Further real-world studies are needed to optimize patient selection and treatment sequencing.

Source: Cancer Medicine

DOI: 10.1002/cam4.72457