The efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-positive and -low metastatic breast cancer with brain metastases (BCBM): A retrospective, multicenter, real-world study.

Abstract

e13120 Background: Accumulating data demonstrate both overall and intracranial activity of Trastuzumab deruxtecan (T-DXd) in HER2 positive breast cancer brain metastasis (BCBM). Limited data available regarding its efficacy on HER2 low BCBM, as well as patients who have symptomatic active BM, leptomeningeal disease (LMD), and poor performance status. Methods: This multicenter, retrospective, real-world study enrolled patients who were diagnosed with HER2 positive or low BCBM, and received T-DXd treatment. Progression-free survival (PFS), overall survival (OS), intracranial progression survival (IC-PFS), objective response rate (ORR), disease control rate (DCR), IC-ORR, IC-DCR and adverse events (AEs) were evaluated. Results: From January 2021 toNovember 2024, 58 HER2 positive patients and 30 HER2 low patients were enrolled in the study. In the HER2 positive cohort, the median PFS, IC-PFS, and OS were 12, 15, and 46 months, respectively. The ORR, DCR, IC-ORR, and IC-DCR based on RECIST 1.1 were 65.2%, 91.3%, 61.0%, and 90.2%, respectively. According to RANO-BM, IC-ORR and IC-DCR were 59.5% and 88.1%. HR expression showed no impact on efficacy. In HER2-low cohort, the median PFS, IC-PFS, and OS were 5, 18, and 26 months, respectively. The ORR, DCR, IC-ORR, and IC-DCR based on RECIST 1.1 were 38.1%, 85.7%, 44.4%, and 85.7%, with no CNS progression at data cutoff. According to RANO-BM criteria, IC-ORR and IC-DCR were 44.4% and IC-DCR 94.4%. HR positive subgroup showed significantly better survival outcomes than HR negative subgroup, the overall PFS, and CNS PFS, with 15 months vs. 4 months (P = 0.0027) and 18 months vs. 4 months (P = 0.012), respectively. 4 patients had isolated LMD and 12 had both brain metastases and LMD, the median IC-PFS was 16 months. T-DXd was well tolerated, the most common AEs included fatigue (45.9%), nausea (11.4%) and appetite loss (25.2%). Interstitail lung disease (ILD) occurred in 6 (6.7%) patients, with only 1 patients diagnosed with grade 3 ILD, and discontinued T-DXd. Conclusions: In conclusion, the present study strongly confirmed the robust intracranial efficacy of T-DXd BCBM with both HER2 positive and low expression, patients with stable and active disease, with significant symptoms and LMD.