Real-world effectiveness of trastuzumab deruxtecan in heavily pretreated her2-positive metastatic breast cancer: A single-center experience

Aim: Trastuzumab deruxtecan (T-DXd) has shown substantial activity in trials of HER2-positive metastatic breast cancer (mBC), but real-world data in heavily pretreated patients, in those with CNS metastases, and in patients started at reduced doses remain limited. To evaluate real-world efficacy and safety of T-DXd in HER2-positive mBC, focusing on late-line use, CNS disease, and reduced-dose initiation.Material and Methods: This retrospective single-center cohort included 42 consecutive HER2-positive mBC patients treated with T-DXd between September 2023 and December 2025. HER2 positivity required IHC 3+ or IHC 2+/ISH-positive. Baseline CNS metastases were present in 16 patients (38.1%); 81.0% received T-DXd as fourth-line therapy or later. T-DXd was initiated at 3.6 mg/kg in 34 patients (81.0%) and at 5.4 mg/kg in 8 (19.0%). Primary endpoints were real-world progression-free (rwPFS) and overall survival (rwOS); secondary endpoints were disease control rate (DCR) and safety. Results: At a median follow-up of 16.2 months, median rwPFS was 14.4 months (95% CI: 10.8–18.0) and median rwOS was not reached. ORR was 67.5% and DCR 90.0% (n=40 evaluable). In the CNS subgroup, ORR was 62.5% and rwPFS 13.2 months; in the 3.6 mg/kg subgroup, ORR was 64.7% and rwPFS 14.1 months. Any-grade adverse events occurred in 59.5%, grade ≥3 in 11.9%; ILD/pneumonitis in 4.8% (all grade 1–2).Conclusion: T-DXd showed meaningful, sustained real-world activity in heavily pretreated HER2-positive mBC, including CNS disease and reduced-dose initiation, warranting prospective confirmation.