Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases

Background: Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM. Methods: We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free s...