Pharmacotherapies for the treatment of glioblastoma – current evidence and perspectives

ABSTRACT

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.

KEYWORDS:

• Glioblastoma
• temozolomide
• bevacizumab
• clinical trial
• immunotherapy

Article highlights

• For patients with newly diagnosed glioblastoma, the standard of care remains temozolomide-based radiochemotherapy.

• Phase III data on bevacizumab, cilengitide, and alternative dosing schedules for temozolomide did not show a survival benefit in newly diagnosed glioblastoma.

• For elderly patients with a methylated MGMT promoter, temozolomide alone is probably superior to radiotherapy alone.

• In recurrent disease, no widely accepted standard of care exists. Alkylating chemotherapy either as a rechallenge with temozolomide or nitrosoureas (e.g. CCNU), and bevacizumab are currently used. The combination of bevacizumab with CCNU is not superior for OS to single agent activity of CCNU.

• Phase III data emerging in the next years will define the role of novel immunotherapeutic concepts including checkpoint inhibition and vaccination.

This box summarizes key points contained in the article.

Declaration of interests

M Weller has received research grants from Acceleron, Actelion, Bayer, Isarna, Merck Sharp & Dohme, Merck & Co., Novocure, PIQUR Therapeutics and Roche. He has received honoraria for lectures, advisory board participation or consulting from Celldex, Immunocellular Therapeutics, Insarna, Magforce, Merck Sharp & Dohme, Merck & Co., Northwest Biotherapeutics, Novocure, Pfizer, Roche and Teva. K Seystahl has received honoraria from Roche for advisory board participation. P Roth has received honoraria from Merck Sharp & Dohme, Roche, Novartis and Molecular Partners for advisory board participation or lectures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.