| Abstract: [Objective] To explore the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the real world with human epidermal growth factor receptor 2 (HER2) expression, brain metastasis, and advanced breast cancer, and to explore the predictive marker of T-DXd efficacy. [Methods] The study retrospectively analyzed the clinical and pathological data of 15 patients with HER2 expression and brain metastasis of breast cancer who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2023, evaluated the efficacy and safety of T-DXd, and explored the predictive markers of efficacy of T-DXd. [Results] In this study, the median treatment line of T-DXd was 5 lines, the median progression-free survival (PFS) was 6.0 months, and the objective response rate (ORR) of intracranial tumors was 80%. The correlation between 12 clinical and pathological characteristics and T-DXd PFS was evaluated using the Kaplan-Meier method, including: patient age, estrogen receptor expression, HER2 expression, Ki-67 level, number of metastatic lesions, presence of active brain metastases, Eastern Cooperative Oncology Group performance status, number of T-DXd treatment lines, late-stage treatment with cyclin-dependent kinase 4/6 inhibitors, HER2 targeted therapy and antibody-drug conjugate therapy, local radiotherapy for brain metastases. Among these factors, only HER2 expression status and T-DXd PFS were significantly correlated. The mPFS of the HER2 overexpression group was significantly longer than that of the HER2 low expression group (7.0 months vs. 3.5 months, P = 0.016). Multivariate analysis using the Cox model showed that HER2 overexpression was an independent prognostic factor for T-DXd PFS (HR = 0.215, 95% CI 0.054-0.857, P = 0.029). Fisher's exact test indicated that none of the above clinical and pathological factors were significantly associated with the intracranial tumors ORR of T-DXd. The main adverse reactions of T-DXd in this study were: nausea and vomiting, leukopenia, neutropenia, thrombocytopenia, anemia, fatigue, etc., with a low incidence of grade 3 or above adverse reactions. [Conclusion] T-DXd has a high intracranial tumors ORR in breast cancer patients with HER2 expression and brain metastasis. HER2 overexpression can be used as a predictive marker of PFS benefits of T-DXd, but it has no significant correlation with the intracranial tumors ORR of T-DXd. T-DXd has good tolerance. |
