CLTR-08 TREATMENT STRATEGIES IN METASTATIC BREAST CANCER PATIENTS WITH LEPTOMENINGEAL DISEASE – A PROSPECTIVE OBSERVATIONAL REGISTRY STUDY
Angelika M Starzer, Katheryn Santos, Craig Snow, Catherine Stever, Sanjana Ravikumar, Rebecca Ottesen, Katie Joanna Ziko, Alyssa Martin, Casey Kain, Georgia Suggs, Lynette M Sholl, Sara M Tolaney, Carey Anders, Nancy U Lin, Sarah SammonsAbstract
Background
Leptomeningeal disease (LMD) in metastatic breast cancer (MBC) patients (pts) remains a therapeutic challenge and is associated with a poor prognosis. Data on the efficacy of novel CNS-active agents, such as trastuzumab deruxtecan (T-DXd), in this setting are limited.
Methods
We are conducting a prospective observational registry that accrues MBC pts with LMD after giving informed consent. We collect clinical data as well as blood and cerebrospinal fluid (CSF) samples. Descriptive analyses were conducted on the cohort enrolled to date. We report time-on-treatment with T-DXd calculated with Kaplan–Meier estimation using SPSS.
Results
To date, 28 women with MBC (14 [50%] HR+/HER2-, 2 [7.1%] HR+/HER2+, 5 [17.9%] HER2+/HR-, 7 [25%] triple-negative) diagnosed with LMD (median age at LMD diagnosis 53 years [range 32-70]) have been accrued. The median time from MBC to LMD diagnosis was 22 months (range 0-90). As first-line treatment approach for LMD, 13 (46.4%) pts received radiation, followed by systemic therapy in 10 (35.7%) pts, while 15 (53.6%) pts received systemic therapy only. Fourteen (50%) pts were treated with T-DXd after LMD diagnosis, of which 9 pts were classified as HER2-low (HER2 IHC 1+ or 2+ FISH negative). Eight pts discontinued T-DXd for disease progression and two for toxicity, while four pts remain on T-DXd. The median time-on-treatment with T-DXd was 6.0 months (95% CI 2.3-9.7). Seven of 14 (50%) pts treated with T-DXd were deceased. CSF was collected in 13/28 (46%) pts of which 7 had successful NGS testing of CSF. Targetable genomic alterations were detected in 6/7 pts.
Conclusions
In this prospective registry, T-DXd demonstrated encouraging activity in MBC pts with LMD, including the HER2-low subset. We show the feasibility of CSF-based molecular profiling to identify actionable alterations in LMD.