431PBEVACIZUMAB AND FOTEMUSTINE FOR RECURRENT HIGH GRADE GLIOMAS

Abstract Aim: Primary tumours of the central nervous system account for approximately 3% of all cancers. High-grade gliomas (HGG) account for 70% of all gliomas and include anaplastic astrocytomas, anaplastic oligoastrocytomas and anaplastic oligodendrogliomas (WHO grade III), as well as glioblastomas (WHO grade IV). Median survival is 12-18 months for WHO grade IV and 2 to 5 years for WHO grade III. At recurrence there is no accepted standard of care. Recent phase II trials have demonstrated activity of nitrosoureas such as fotemustine (FTM) in recurrent HGG. Bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor, is the first antiangiogenic agent with documented activity in HGG. Methods: We have investigated the role of the combination of FTM and bevacizumab in glioblastoma (GBM) and WHO grade III gliomas (non-GBM) at first recurrence after prior therapy. From January 2011 to January 2014, data of 30 patients were collected. From recurrence, we estimated 6-month progression-free survival (PFS-6), overall survival (OS) and toxicities therapies-related. The treatment consisted of an induction phase with FTM at 75 mg/m2 intravenously on day 1, 8 and 15 and bevacizumab at 10 mg/kg intravenously on day 1 and 15, followed after an interval of 4-5 weeks by a maintenance phase with bevacizumab at 10 mg/kg every 2 weeks and FTM at 75 mg/m2 every 3 weeks until tumour progression or unacceptable toxicity. Patients who required progressive FTM dose reductions received bevacizumab alone. Results: The median time from original diagnosis to recurrence was 13 months for GBM and 35 months for non-GBM gliomas. All patients completed the induction phase and a median of 11 maintenance cycles were administered for GBM and 13 cycles for non-GBM patients. PFS-6 rate was 45% for GBM and 67% for non-GBM; median OS was 14 months for GBM and 21 months for non-GBM patients. Most patients experienced grade 1 toxicities (hypertension, fatigue, proteinuria); grade 2 toxicities were predominantly hematologic (thrombocitopenia). Conclusions: In our study the combination of FTM and bevacizumab was well tolerated and PFS-6 and OS confirmed published literature. Further studies are needed to demonstrate the benefit of this combination in the treatment of recurrent HGG. Disclosure: All authors have declared no conflicts of interest.