Wen PY, et al. - Since phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas, researchers examined pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with PI3K pathway–activated glioblastoma at first or second recurrence. They assessed PI3K pathway inhibition in tumor tissue and buparlisib pharmacokinetics in cohort 1 (n = 15), that comprised patients scheduled for re-operation after progression and were given buparlisib for 7 to 13 days before surgery, and 6-month progression-free survival (PFS6) in cohort 2 (n = 50), that included patients not eligible for re-operation and were administered buparlisib until progression or unacceptable toxicity. Once daily oral buparlisib 100 mg was administered on a continuous 28-day schedule. Findings revealed minimal single-agent efficacy of buparlisib and although it achieved significant brain penetration, clinical efficacy was lacking which was explained by incomplete blockade of the PI3K pathway in tumor tissue. Treatment-related grade 3 or greater adverse events which were experienced most commonly were lipase elevation (n = 7 [10.8%]), fatigue (n = 4 [6.2%]), hyperglycemia (n = 3 [4.6%]), and elevated ALT (n = 3 [4.6%]).