INTRODUCTION: Glioblastoma, the most common malignant brain tumor, exhibits a 
poor prognosis with little therapeutic progress in the last decade. Novel 
treatment strategies beyond the established standard of care with 
temozolomide-based radiotherapy are urgently needed.
AREAS COVERED: We reviewed the literature on glioblastoma with a focus on phase 
III trials for pharmacotherapies and/or innovative concepts until December 2015.
EXPERT OPINION: In the last decade, phase III trials on novel compounds largely 
failed to introduce efficacious pharmacotherapies beyond temozolomide in 
glioblastoma. So far, inhibition of angiogenesis by compounds such as 
bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing 
schedules of temozolomide did not prolong survival, neither at primary diagnosis 
nor at recurrent disease. Promising strategies of pharmacotherapy currently 
under evaluation represent targeting epidermal growth factor receptor (EGFR) 
with biomarker-stratified patient populations and immunotherapeutic concepts 
including checkpoint inhibition and vaccination. The clinical role of the 
medical device delivering 'tumor-treating fields' in newly diagnosed 
glioblastoma which prolonged overall survival in a phase III study has remained 
controversial. After failure of several phase III trials with previously 
promising agents, improvement of concepts and novel compounds are urgently 
needed to expand the still limited therapeutic options for the treatment of 
glioblastoma.