Division of Cancer, Imperial College, London, United Kingdom
R. C. Coombes , J. A. Reise , M. Lau , S. C. Carme , G. E. Searle , M. Huiban , P. Burgess , K. Koch , A. Das-Gupta , A. Saleem
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, an open-label, non-randomized study using carbon-11 labeled [11C] lapatinib is performed in patients with HER2+ MBC. A minimum of 10 patients with an ECOG of < 3 into two cohorts: (a) with at least one 1 cm diameter brain metastasis or (b) without brain metastases. Two PET scans are performed in each pt following intravenous administration of a microdose of [11C] lapatinib – (1) in lapatinib -naïve patients and (2) at steady state lapatinib, after treatment with unlabelled oral lapatinib 1500mg OD for 8 days. [11C] lapatinib time-activity curves are generated for normal brain and brain metastases, the PET volume of distribution in brain calculated and penetration of [11C] lapatinib into brain quantified. Analysis of brain PET data is explorative as [11C] lapatinib is a new tracer. Therefore, this study investigates both the difference in lapatinib brain penetration between patients with and without brain metastases, as well as the effect of low and high concentrations of lapatinib on the BBB efflux system.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
First Author: Nicholas Patrick McAndrew
2023 ASCO Annual Meeting
First Author: Elham Vosoughi
2021 ASCO Annual Meeting
First Author: Ian E. Krop
2021 ASCO Annual Meeting
First Author: Constantinos Savva