OBJECTIVES: Trastuzumab Deruxtecan (T-DXd) is an antibody drug conjugate that targets the human epidermal growth factor receptor 2 (HER2). Whether patients were HER2-positive (Destiny 01) or low (Destiny 04), T-DXd had good treatment efficacy in patients with metastatic breast cancer (mBC). However, limited data existed on the real-world effectiveness of T-DXd in Asian populations.

METHODS: We conducted a retrospective cohort study by analyzing electronic medical data from the multi-center Chang Gung Memorial Hospital in Taiwan. We included both HER2-positive and HER2-low mBC patients newly received at least one administration of T-DXd as any line of therapy from April 1, 2022 to December 31, 2023. The effectiveness outcomes were progression free survival (PFS) and overall survival (OS). Baseline characteristics and tumor burden were collected for subgroup analyses.

RESULTS: We total included 68 mBC patients with the following characteristics: a median age of 53.3 years (Q1-Q3：47.1-60.7), 27 patients (39.7%) with an ECOG score of 0, 35 patients (51.4%) HER2-positive, 33 patients (48.5%) Hormone Receptor-positive, 12 patients (17.6%) with brain metastases, and 25 patients (36.7%) with bone metastases. Among all patients with a median of 6.5 months follow-up, the primary outcome of PFS was 8.7 months (95% CI: 5.4 to 11.3) and OS was 11.5 months (8.2 to 18.9). Subsequent analyses revealed that the HER2-positive subgroup had superior PFS (11.0 vs. 6.0 months, P < 0.05) and OS (13.9 vs. 8.7 months, P < 0.05) compared to HER2-low subgroup.

CONCLUSIONS: In clinical trials, PFS was 16.4 months for HER2-positive (Destiny 01) and 9.9 months for HER2-low (Destiny 04). However, our real-world cohort analysis found slightly lower PFS and OS across all patients and in HER2-positive or HER2-low subgroups. This difference may be due to poorer health conditions in real-world patients and economic barriers. Further long-term follow-up is needed to confirm our findings.