102P Breast Cancer Patients Treated with Intrathecal Therapy for Leptomeningeal Metastases: Characteristics and Validation of Prognostic Models in a Large Real-Life Database

Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high rates of morbidity/mortality. Large cohorts are scarce. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. ESME MBC database (NCT03275311) includes all consecutive patients having started treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan-Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. Of 22,266 female patients included in the ESME database covering 2008-2016, 312 were IT-treated with methotrexate, cytarabine or thiotepa and included in our analysis (15 patients have been excluded because of lack of data on the treatment line). Compared with non-IT treated ones, these were younger at MBC relapse (median age 52 years vs 61 years) and had more often lobular histology (23.4% vs 12.7%) or triple-negative subtype (24.7% vs 13.3%) (all p<0.001). Median OS was 4.5 months (95% CI 3.8-5.6) and 1-year survival rate was 25.6%. In case of IT therapy, significant prognostic factors associated with worse outcome by multivariable analysis were triple-negative subtype (HR=1.81 [95%CI 1.32-2.47]), treatment line ≥ 3 (HR=1.88 [95% CI 1.30-2.73]), ≥ 3 other metastatic sites (HR=1.33 [95%CI 1.01-1.74]), and IT cytarabine or thiotepa vs methotrexate (HR=1.68 [95%CI 1.28-2.22]), while concomitant systemic therapy was associated with better OS (HR=0.47 [95%CI 0.35-0.62]) (all p<0.001). We validated two previously published prognostic scores, the Curie score and the breast graded prognostic assessment, both with C-index of 0.57. MBC patients with LM treated with IT therapy have a poor prognosis. However, in this large series, we could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used.