THER-12. PRECLINICAL EVALUATION OF NERATINIB PLUS T-DM1 IN ORTHOTOPIC PDX MODELS OF HER2-POSITIVE BREAST CANCER BRAIN METASTASES

ABSTRACT: Abstract Breast cancer brain metastases (BCBM) are a major cause of morbidity and mortality, despite multimodal management including surgery, radiotherapy, and systemic therapies. There is an urgent need to develop novel, efficacious alternatives. Neratinib is an orally bioavailable, irreversible pan-HER tyrosine kinase inhibitor that is FDA-approved in the extended adjuvant treatment setting for HER2-positive, early breast cancer (NCT00878709). Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate with reported single-agent activity against HER2-positive BCBM. Here, we used HER2-positive orthotopic patient derived xenograft (PDX) models of BCBM to test if combining neratinib with T-DM1 could improve tumor response. PDX cells are labelled with luciferase to allow tumor growth mea

SUBMITTER: Ni J 

PROVIDER: S-EPMC7213268 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature