Survival outcomes with low-dose bevacizumab compared to standard dose regimens in recurrent glioblastoma

Nicholas Avgeropoulos, George Avgeropoulos, Garrett Riggs, Christopher Reilly
MD Anderson Cancer Center, Orlando, Orlando, FL, USA

BACKGROUND: Glioblastoma (GB), the most common and aggressive primary malignancy of brain, portends a dismal prognosis marked by rapidly progressive clinical deterioration. Bevacizumab (BV; Avastin), a US FDA approved humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has demonstrated significant efficacy in patients with recurrent GB at 10 mg/kg every 14 days either as a single agent or in combination with carboplatin or irinotecan. OBJECTIVE: This review compares the efficacy of low-dose BV (5mg/kg) administered as a single agent or in combination / tandem with other chemotherapies against survival expectations of standard dose / schedule. DESIGN: Retrospective cohort study. METHODS: A single institution retrospective review was conducted on all patients with recurrent GB treated from January 2009 - May 2013. A subset of 48 patients with radiographically recurrent GB were placed on bevacizumab 5 mg/kg therapy every 2 weeks as a practice parameter. All patients had diagnostic surgery and temozolomide-based chemoradiation. The primary endpoint was median/mean overall survival (OS). RESULTS: Single-agent BV at 10 mg/kg or greater in patients with recurrent GB (control database): median OS 8.63 months (95%CI, 8.54-8.72 months). Review cohort: median OS 14 months (95%CI, 10-16 months); mean OS 19.2 months. Patients' first BV injection at >6 months from time of glioblastoma diagnosis was associated with a death hazard ratio of 2.27 (p=0.041) using a multivariate Cox proportional hazards model. CONCLUSION: Our results suggest that administration of BV administered for treatment of rec/prog GB at 5 mg/kg every two weeks or less (in dose / frequency) is not inferior to standard dosing. There may be a survival advantage of low-dose (5 mg/kg) BV when compared against BV at 10 mg/kg every two weeks.