Approximately 30% to 50% of patients with human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer will develop brain metastases. Unfortunately, once local therapies such as radiosurgery and/or radiotherapy cease to be effective, there are no defined standard therapies for these patients.
Further complicating treatment for these patients, most drugs do not cross the blood brain barrier, making systemic chemotherapy and targeted therapies extremely limited for treating brain metastases. These patients are also often excluded from breast cancer trials because of the presence of their brain metastases, which ultimately makes the potential benefit of new treatments for this group unclear. Therefore, there is a direct need for trials designed specifically for this patient population.
The recent success of Trastuzumab Deruxtecan (T-DXd) in the Destiny-Breast01 trial for patients with and without central nervous system metastases, and the clear unmet need for these patients lead to MEDSIR designing the DEBBRAH trial. This trial will assess the efficacy of T-DXd for HER2+ or HER low-expressing metastatic breast cancer with brain metastases and/or leptomeningeal carcinomatosis. This phase 2, open-label, single arm trial will enroll 39 patients in 5 cohorts in Spain and Portugal.
Preliminary results were shared in a spotlight session at the 2021 San Antonio Breast Cancer Symposium. In cohort 1, 87.5% of patients had stable brain metastases and were alive without progressive disease at 16 weeks. (p < 0.001) Additionally, at the data cutoff, 62.5% had not progressed or died. In cohort 3, an intracranial objective response rate (ORR-IC) was reported in 3 patients (44.4% [95% CI 13.7-78.8], (p <0.001)). 1 patient had a stable disease lasting at least 24 weeks. At data cutoff, 44.4% of patients in cohort 3 had not progress or died. The treatment also demonstrated a favorable safety profile with adverse events occurring in ³ 20% of patients in cohorts 1-5.
The preliminary results are promising, and additional follow-up and data from remaining cohorts will help guide the use of T-DXd in HER2+ and HER low-expressing advanced breast cancer with brain metastases and/or leptomeningeal carcinomatosis.
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