P. Wen, W. Yung, I. Mellinghoff
May 20, 2014
Citations
1
Influential Citations
16
Citations
Journal
Journal of Clinical Oncology
Abstract
2019 Background: The PI3K pathway is activated in most GBMs and represents a potential therapeutic target. Buparlisib is an oral, pan-Class I PI3K inhibitor that enters the brain at therapeutic concentrations and inhibits the growth of U87 and GBM PDX models. Methods: The Ivy Consortium conducted a phase II study of buparlisib in recurrent GBM patients with activation of the PI3K pathway (mutation, homozygous deletion or loss of immunohistochemistry (IHC) of PTEN, PIK3CA or PIK3RI mutations, or detectable pAKT). Additional eligibility criteria included radiologic progression, 1st or 2nd relapse, > 18 yrs, KPS > 60, adequate bone marrow and organ function, no prior bevacizumab or enzyme-inducing antiepileptic drugs. Patients received buparlisib 100mg daily. The study consisted of 2 concurrent cohorts. In Cohort 1 (up to 15 patients) buparlisib was given for 8-12 days prior to surgery for recurrent disease. Patients underwent FDG PET, pharmacokinetic studies, and tumor obtained for drug concentrations and p...