NCOG-60. Trastuzumab-deruxtecan for the management of leptomeningeal metastases from breast cancer

Retrospective data has suggested benefit of targeting Human Epidermal Growth Factor Receptor 2 (HER2) with an antibody drug conjugate such as trastuzumab-deruxtecan (T-DXd) in patients with leptomeningeal metastases (LM), but real-world data remains limited. We performed a retrospective chart 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. 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. In the initial pathology, estrogen receptor (ER) was positive in 68.3% of patients in the initial breast biopsy, progesterone receptor (PR) was positive in 56.3%, and HER2 was low in 37.5%. Sixty-eight percent had a prior histology sample at any time with low HER2. LM directed therapy included whole brain radiation (45.75%), local radiation (37.5%), craniospinal radiation (18.76%), and intrathecal (IT) chemotherapy (18.75%). IT chemotherapy included topotecan with trastuzumab, cytarabine with trastuzumab, and topotecan alone. Six patients were still on T-DXd at the time of our analysis, and 9 patients had died. Median time on T-DXd was 5.6 months (CI 0 -17.5). Median time to LM diagnosis was 45.7 months (CI 24.2-67.19). Eleven patients survived more than 6 months after LM diagnosis, and 8 over 12 months. Survival after LM diagnosis is increasing with novel therapy and our findings highlights 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.