Abstract

TPS107 Background: Patients with HER2+ breast cancer tend to develop visceral metastases. Several anti-cancer agents including trastuzumab are not believed to readily cross the blood-brain barrier (BBB); hence, central nervous system (CNS) disease progression is emerging as an important clinical problem in this patient population. Although preclinical data suggest that lapatinib brain concentrations are low in healthy animals, probably due to the BBB efflux transporters, observations from clinical studies suggest lapatinib treatment might be associated with reduced CNS tumor growth. One hypothesis is that disruption of the BBB by tumors circumvents the usual protective function of transporters or that inhibition of efflux transporters by lapatinib enhances accumulation upon repeat dosing. The role of lapatinib in prevention of brain metastases is currently explored in a Phase III trial, EGF 111438 (CEREBREL). Methods: In order to directly assess if lapatinib penetrates into the brain and brain metastases,...

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