Tratuzumab deruxtecan: A real-world study in the treatment of metastatic breast cancer in China.

e13095 Background: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) that has demonstrated improved survival in patients with metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer in clinical trials. In 2022, the FDA has approved T-DXd for the treatment of adult patients with unresectable or metastatic breast cancer (mBC). However, real-world evidence regarding the efficacy of T-DXd remains limited. Methods: We retrospectively collected clinical and demographic data from HER2-low mBC patients who were treated with T-DXd across various treatment lines between November 2021 and November 2024 at Fudan University Shanghai Cancer Center. Real-world progression-free survival (PFS) was estimated using the Kaplan-Meier method. Treatment response was assessed according to RECIST 1.1 criteria. Results: A total of 128 patients with mBC received T-DXd during the study period. All patients were Chinese females, with a median age of 55.92 years (range: 33 to 81) and a median metastases number of 2 (range: 1 to 7). Among these, 10 (7.81%) had HER2-0 mBC (i.e., triple-negative), and 118 (92.19%) had HER2-low mBC, including 79 (61.72%) with hormone receptor-positive (HR+) and 39 (33.05%) with hormone receptor-negative (HR-) status. The median number of treatment lines prior to T-DXd in HER2-low mBC patients was 3 (range: 2 to 5), with the median pre-treatment line being 4 in HR+ patients and 3 in HR- patients. In HER2-low mBC patients, the median PFS was 10.4 months (95% CI: 7.397 to 13.403) after initiating T-DXd. For HR+ and HR- HER2-low patients, the median PFS was 8.47 and 11 months, respectively. Additionally, 80.53% of HER2-low patients received no more than 4 lines of treatment prior to T-DXd, and their median PFS was significantly higher compared to those who received at least 5 treatment lines (13.27 vs. 7.20 months, p < 0.05). Furthermore, among HR+ HER2-low patients, the proportion of progressive disease (PD) patients with brain metastases was significantly higher than that of those without brain metastases (54.55% vs. 14.71%, p < 0.01). Conclusions: Our research evaluates the real-world efficacy of DS8201 treatment in HER2-low mBC patients within the Chinese population. Earlier administration of T-DXd is recommended to improve survival outcomes in HER2- low mBC patients. The prolonged PFS observed in HR- HER2-low patients, compared to HR+ patients, may be attributed to the earlier initiation of DS8201 in triple-negative patients. Further investigation with a larger cohort and prospective analysis of HER2-low mBC patients is needed. Characteristics of the HER2-low patients at baseline. Characteristic HER2-low Patients Median age (range) - yr 55.92 (33-81) Female sex - no. (%) 118 (100%) HER2-low status - no. (%) IHC 1+ 65 (55.08%) IHC 2+ and ISH-negative 53 (44.92%) HR-positive - no. (%) 39 (33.05%) HR-negative - no. (%) 79 (66.95%)