Real-world safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive/HER2-low metastatic breast cancer: a multicenter retrospective cohort study

The efficacy of trastuzumab deruxtecan (T-DXd) has been demonstrated in large, phase III studies in HER2-positive (HER2+) and HER2-low metastatic breast cancer. Nevertheless, real-world data on T-DXd use are still limited. Patients with HER2+ or HER2-low metastatic breast cancer treated in six tertiary hospitals in Greece between September 2021 and May 2025 were included. Objective response rate, real-world progression-free survival (rwPFS), overall survival (rwOS), and safety were assessed. Ninety-seven patients were included in the analysis; 49 had HER2+ and 48 had HER2-low disease. In the HER2+ cohort, median rwPFS was 14.9 months (95% Confidence Interval CI, 10.97- not reached NR) and median rwOS was NR; rwPFS was shorter in patients with brain metastases (10.9 months vs 37.5 months, HR 3.28, p = 0.03). In the HER2-low cohort, rwPFS was 6.1 months (95% CI, 5.43-10.5) and rwOS was 14.1 months (95% CI, 9.6-NR). The rate of TRAEs was 41.1%; the rate of pneumonitis/interstitial lung disease was 6.7%. Dose interruptions and treatment discontinuation were reported in 4.4% and 1.1% cases, respectively. Our study confirms the efficacy and safety of T-DXd in daily clinical practice. Further research and longer patient follow-up are needed to elucidate optimal therapy sequencing.