Hit: A Multicenter Phase I-Ii Study Of Trastuzumab Administered By Intrathecal Injection For Leptomeningeal Meningitis Of Her2+Metastatic Breast Cancer.

TPS662 Background: Leptomeningeal metastases (LM) are commonly associated with breast cancer (BC), announcing short term prognosis that intrathecal (IT) chemotherapy poorly modifies. Incidence is particularly marked in HER2+ tumours. With the better control of extra-cerebral disease and prolonged survival yielded by intra-venous (IV) trastuzumab (T), the main hypothesis is that intra-cerebral recurrences are not reached by this high molecular weight (148 kD) monoclonal antibody. Analyses performed in cerebrospinal fluid (CSF) following IV T have shown low T levels, suggesting that LM of HER2+ BC would remain potentially sensitive to anti-HER2 agents as long as they could by-pass the meningeal blood brain barrier. Intraventricular (via Ommaya port) or IT administration of T would allow keeping control on LM progression through high T therapeutic concentrations in CSF. This prospective trial is the first phase I-II study sponsored by Institut Curie to investigate the safety and efficacy of the IT administra...