EFFECTIVENESS OF CAPECITABINE FOR PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS FROM BREAST CANCER ACCORDING TO IMMUNOHISTOCHEMICAL SUBTYPE

Background: Leptomeningeal carcinomatosis (LC) is associated with poor prognosis among different neoplasia. In breast cancer (BC), data on the activity of systemic therapy in this scenario is scarce. Capecitabine is often selected as a regimen for central nervous system (CNS) metastases from BC in clinical practice. Objective: We aimed to evaluate its effectiveness for LC in the different immunohistochemical (IHC) subtypes of BC. Methods: This single-center retrospective study evaluated patients (pts) with BC and LC that received capecitabine from 2010 to 2021. LC diagnosis was established based on positive oncotic cytology in the cerebrospinal fluid or brain imaging findings. Study endpoints were intracranial progression-free survival (CNS-PFS), overall survival (OS), intracranial response rate (CNS-ORR), and intracranial disease control rate (CNS-DCR) at 3 months, according to the IHC BC subtype. Cox regression was used to evaluate factors associated with CNS-PFS and OS. Results: Among 50 pts included, 29 had LC and parenchymal disease, and 21 had LC alone. Thirty-two pts (64%) had hormone receptor-positive HER2-negative (HR+HER2-) BC, 8 (16%) HER2-positive (HER2+) BC, and 10 (20%) triple-negative BC (TNBC). Half of the pts (48%) had ECOG-PS 0-1 at the time of the diagnosis of CNS metastases, and most pts (78%) received brain radiation therapy. Thirty pts were evaluable for response rates at 3 months. Although pts with TNBC had numerically higher CNS-ORR (50% versus 20% for HER2+ and 23,8% for HR+HER2 BC, the 3-month CNS-DCR were higher in HR+HER2- and HER2+ BC, 90,5% and 80%, respectively, versus 50% for TNBC. No difference was observed in CNS-ORR and CNS-DCR between pts with LC alone compared to those with both LC and parenchymal disease. BC subtype was the only factor identified as related to survival outcomes. TNBC pts with LC treated with capecitabine had worse CNS-PFS (HR 6.22, 95% CI 2.49-15.53, P<0.001) and OS (HR 3.94, 95% CI 1.69-9.19, P=0.001) compared to HR+HER2- pts. Median CNS-PFS was 8.3 mo in HR+HER2-BC, 3.5 mo in HER2+BC, and 1.7 mo in TNBC. Median OS was 10.3 mo, 5 mo, and 2.6 mo, respectively. Conclusions: Although LC from BC is associated with poor prognosis, some patients might benefit from systemic treatment with capecitabine. Higher CNS-DCR were observed in HR+HER2- and HER2+ pts, while pts with TNBC had extremely unfavorable outcomes. Better treatment strategies for pts with LC are urgently needed regardless of the BC subtype.