Real-world clinical outcomes of trastuzumab deruxtecan in patients with HER2-low metastatic breast cancer

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) approved for HER2-low metastatic breast cancer (mBC), showing improved survival outcomes in clinical trials. However, real-world evidence on its effectiveness among Chinese patients remains limited. Patients with HER2-low mBC who received T-DXd at Fudan University Shanghai Cancer Center between November 2021 and November 2024 were retrospectively enrolled. Clinical and demographic data were extracted from medical records. Real-world progression-free survival (rwPFS) was estimated using the Kaplan-Meier analysis. Tumor response was assessed radiologically according to RECIST 1.1 criteria. An exploratory prognostic score was derived using coefficients from multivariable Cox regression. A total of 126 Chinese female patients were enrolled, with a median age of 56 years (IQR: 48–64). De novo metastatic disease was present in 40 patients (31.75%), whereas 86 patients (68.25%) had recurrent metastatic disease. Hormone receptor (HR) status was positive in 82 (65.08%) patients and negative in 44 (34.92%). The median number of prior treatment lines was 3 (IQR: 2–5). The median rwPFS was 9.1 months. A median PFS of 3.5 months was observed during the immediately preceding treatment and is provided solely as descriptive clinical context. In HR-positive patients, those with low PR expression (≤ 10%) had significantly longer rwPFS than those with high PR expression (17.77 vs. 6.13 months; p < 0.01). Among 111 patients with response-evaluable disease, the objective response rate (ORR) was 30.63%, and the disease control rate (DCR) was 72.07%. In an exploratory analysis, a cohort-derived score based on age, HER2 status, and HR status separated patients into low- and high-score groups, with median rwPFS of 12.4 and 5.13 months, respectively (p < 0.01). In this real-world cohort of Chinese patients with HER2-low mBC, T-DXd showed encouraging real-world antitumor activity and survival outcomes. The exploratory score findings should be regarded as hypothesis-generating and require confirmation in independent cohorts. T-DXd showed encouraging real-world antitumor activity in HER2-low metastatic breast cancer. Exploratory analyses identified clinical factors potentially associated with rwPFS during T-DXd treatment.