Wen PY, et al. - In this study including 65 patients with recurrent glioblastoma with phosphatidylinositol 3-kinase (PI3K) pathway activation, researchers tested buparlisib (the pan-PI3K inhibitor) in terms of pharmacokinetics, pharmacodynamics, and efficacy. Cohort 1 comprised of patients scheduled for re-operation following progression, these subjects were given buparlisib for 7 to 13 days before surgery. Until progression or unacceptable toxicity, buparlisib was given to patients not eligible for re-operation included in the cohort 2. On a continuous 28-day schedule, participants received once-daily oral buparlisib 100 mg. In cohort 1, PI3K pathway inhibition in tumor tissue and buparlisib pharmacokinetics were assessed and in cohort 2, 6-month progression-free survival (PFS6) was evaluated (primary end points). In patients with PI3K-activated recurrent glioblastoma, minimal single-agent efficacy was displayed by buparlisib. It lacked clinical efficacy despite achieving remarkable brain penetration. Incomplete blockade of the PI3K pathway in tumor tissue explained the lack of clinical efficacy.