Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and/or leptomeningeal disease (ROSET-BM)

Abstract

Therapeutic options for breast cancer patients with brain metastases (BM)/leptomeningeal carcinomatosis (LMC) are limited. Here, we report on the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2-positive breast cancer patients with BM. Data were analyzed for 104 patients administered T-DXd. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, and IC-PFS were evaluated. ORR by investigator assessment was 55.7% (total population). Median PFS was 16.1 months; 12-month OS rate was 74.9% (total population). Median time-to-treatment failure was 9.7 months. In 51 patients with BM imaging, IC-ORR and median IC-PFS by independent central review were 62.7% and 16.1 months, respectively. In 19 LMC patients, 12-month PFS and OS rates were 60.7% and 87.1%, respectively. T-DXd showed effectiveness regarding IC-ORR, IC-PFS, PFS, and OS in breast cancer patients with BM/active BM, and sustained systemic and central nervous system disease control in LMC patients.Trial Registration: UMIN000044995.

Fig. 1. Patient disposition.

¹This is the result of a survey by Daiichi Sankyo Co., Ltd. of ENHERTU^® purchases at medical institutions and is not information from medical institutions. ²No brain imaging data were submitted: 1 patient. No brain imaging data after initiation of T-DXd were available: 14 patients. BC breast cancer, BM brain metastasis, T-DXd trastuzumab deruxtecan.

Fig. 2. PFS, OS, and TTF (total population).

a PFS, (b) OS, (c) TTF. CI confidence interval, mo month, OS overall survival, PFS progression-free survival, TTF time-to-treatment failure.

Fig. 3. Waterfall plot of change in tumor size of the brain lesion (brain imaging population).

^aHuman epidermal growth factor receptor 2 immunohistochemistry is not 3+, unknown, or missing. L leptomeningeal carcinomatosis, W whole brain radiotherapy within 30 days.

Fig. 4. PFS and OS by classification of BM (total population).

a PFS, (b) OS. ¹Active (not including whole brain radiotherapy within 30 days). ²Stable + Active with whole brain radiotherapy within 30 days. ³Active with LMC/LMC only. ⁴Of the 104 patients, 6 patients with brain imaging data at baseline were not classified by Independent Central Review. BM brain metastasis, CI confidence interval, LMC leptomeningeal carcinomatosis, mo months, OS overall survival, PFS progression-free survival.