Glioblastoma (GBM) is a near fatal, end-stage, disease. According to the Central Brain Tumor Registry of the United States (CBTRUS), GBM is the third most commonly reported histology (14.9% of cases) of all brain and central nervous system (CNS) tumors and the most common of all malignant CNS tumors. Newly-diagnosed GBM patients have a median overall survival (OS) of 12 to 15 months and 2-year overall survival (OS) rate of up to 27%. Glioblastoma is primarily diagnosed in older patients (median age of 64.0 years), with a 5-year survival rate of 5.5% in the most recently reported time period (2009 to 2013).

The current standard-of-care treatment is based on surgical resection (craniotomy) to remove as much of the tumor as is feasible. However, a true gross total resection is never possible, due the significant portion always remaining because of the invasive nature of GBM, which grows down the white myelin sheaths deeper into the brain. Resection is followed by radiotherapy and, depending on methylation status of a deoxyribonucleic acid (DNA) repair protein (06-methylguanine-DNA-methyltransferase [MGMT]), addition of the concomitant adjuvant temozolomide. For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median OS of 6 to 7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is reported as being as short as 3 to 5 months.

Under the current standard of care, a relatively favorable prognosis is correlated with the methylation status of MGMT, isocitrate dehydrogenase isoform 1 (IDH1) status, and lower patient age. Because temozolomide is an alkylating agent that damages DNA, methylation, which silences MGMT, interferes with DNA repair, and improves the tumor’s sensitivity to temozolomide. Tumors with gain-of-function mutations in IDH1 are associated with more favorable outcomes than those with the normal ‘wild-type’ counterparts. In addition, younger age correlation with enhanced survival is attributed to the constellation of the population’s lack of comorbidities and improved ability to weather neurological changes produced by the cancer, its treatment, and surgery.

In summary, there is no doubt that recurrent or progressive GBM constitutes a serious medical condition with a very poor prognosis, even with current standard of care.