Trastuzumab-deruxtecan for the management of leptomeningeal metastases from breast cancer.

Abstract

e14033 Background: Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with an antibody drug conjugate such as trastuzumab-deruxtecan (T-DXd) may be beneficial in patients with leptomeningeal metastases (LM), with limited real-world data. Methods: We performed a retrospective review at the University of Texas MD Anderson Cancer Center for patients with LM and breast cancer in the past 5 years and found a total of 133 patients. We selected only cytology proven LM (33 patients) and then analyzed the patients that were treated with T-DXd after their LM diagnosis was made. Results: We analyzed 16 patients, all females. Median age of 49 years at LM diagnosis, with 50% white, and 93.8% non-Hispanic. Invasive ductal carcinoma was the histology in 68.8% of patients with 31.3% of invasive lobular carcinoma. All patients had brain metastases. Estrogen receptor (ER) was positive in 75% of patients, progesterone receptor (PR) was positive in 56.3%, HER2 was positive in 31.3%, and HER2 was low in 68.8%. Prior to receiving T-DXd 37.5% had received chemotherapy, and 25% had received endocrine therapy. LM directed therapy included whole brain radiation (43.8%), local radiation (37.5%), proton craniospinal radiation (18.8%), and intrathecal (IT) chemotherapy (18.8%). IT chemotherapy included topotecan with trastuzumab, cytarabine with trastuzumab, and topotecan alone. Response rate at first neuroaxis MRI after starting T-DXd was 66% (10 patients, two with complete response and 8 with partial response). Six patients were still on T-DXd at the time of our analysis, and 9 patients had died. Median time on T-DXd was 6.8 months (IQR: 2.7-12.0 months). Median time to LM diagnosis was 46.5 months (IQR 24.6-124.0 months). Eleven patients survived more than 6 months after LM diagnosis, and 8 over 12 months. Conclusions: Survival after LM diagnosis is increasing with novel therapy and our findings highlight the role of T-DXd even in the setting of low HER2. Our findings provide a single center experience in using trastuzumab-deruxtecan for LM in breast cancer patients.