BACKGROUND: This study's primary objective was evaluation of the 
progression-free survival rate at 6 months (PFS-6) in patients with newly 
diagnosed glioblastoma without O(6)-methylguanine-DNA-methyltransferase (MGMT) 
promoter hypermethylation postsurgically treated with enzastaurin before and 
concomitantly with radiation therapy, followed by enzastaurin maintenance 
therapy. PFS-6 of at least 55% was set to be relevant compared with the data of 
the EORTC 26981/22981 NCIC CE.3 trial.
METHODS: Adult patients with a life expectancy of at least 12 weeks who were 
newly diagnosed with a histologically proven supratentorial glioblastoma without 
MGMT promoter hypermethylation were eligible. Patients were treated with 
enzastaurin prior to, concomitantly with, and after standard partial brain 
radiotherapy. Here we report on a multicenter, open-label, uncontrolled phase II 
study of patients with newly diagnosed glioblastoma without MGMT promoter 
hypermethylation treated with enzastaurin and radiation therapy within 4 study 
periods.
RESULTS: PFS-6 was 53.6% (95% confidence interval [CI]: 39.8-65.6). The median 
overall survival was 15.0 months (95% CI: 11.9-17.9) for all patients, 3.9 
months (95% CI: 0.8-9.0) for patients with biopsy, 15.4 months (95% CI: 
10.1-17.9) for patients with partial resection, and 18.9 months (95% CI: 
13.9-28.5) for patients with complete resection. The safety profile in this 
study was as expected from previous trials, and the therapy was well tolerated.
CONCLUSIONS: PFS-6 missed the primary planned outcome of 55%. The secondary 
exploratory analysis according to resection status of the different subgroups of 
patients with biopsies, partial resection, and complete resection demonstrates 
the strong prognostic influence of resection on overall survival.