Highlighting the need for reliable clinical trials in glioblastoma.

INTRODUCTION: Several recent phase III studies have attempted to improve the dismal survival seen in glioblastoma patients, with disappointing results despite prior promising phase II data. Areas covered: A literature review of prior phase II and phase III studied in glioblastoma was performed to help identify possible areas of concern. Numerous issues in previous phase II trials for glioblastoma were found that may have contributed to these discouraging outcomes and discordant results. Expert commentary: These concerns include the improper selection of therapeutics warranting investigation in a phase III trial, suboptimal design of phase II studies (often lacking a control arm), absence of molecular data, the use of imaging criteria as a surrogate endpoint, and a lack of pharmacodynamic testing. Hopefully, by recognizing prior phase II trial limitations that contributed to failed phase III trials, we can adapt quickly to improve our ability to accurately discover survival-prolonging treatments for glioblastoma patients.