P08.46 Rechallenge with bevacizumab in a long-term survivor with glioblastoma

Abstract

The prognosis of patients with glioblastoma multiforme (GBM, WHO grade IV), the most common primary brain tumor in adults, is generally poor with median survival of less than one year in untreated patients and approximately 15 months following standard of care therapy. However, 10 % survival at 5 years was observed in a randomized phase III study. At GBM recurrence, the addition of bevacizumab (BEV), a humanized monoclonal antibody against circulating vascular endothelial growth factor (VEGF), resulted in a 3-4 month prolongation of progression-free survival (PFS) without improving overall survival (OS). A 45-year-old female who underwent surgery for left fronto-temporal WHO grade II astrocytoma associated with epilepsy in 2005, 125I seed implantation at disease progression in 2009 and seed explantation 9 months later, was diagnosed with MGMT methylated GBM on the occasion of partial tumor resection in 2010 followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) chemotherapy, which was stopped after 4 months due to resection of a left temporal tumor cyst and recurrent cyst within 1 month. TMZ treatment causing prolonged thrombocytopenia was discontinued after 1 additional cycle. Immediately after this cycle, the patient experienced left median cerebral artery stroke resulting in right hemianopia, Broca's aphasia and severe hemiparesis of the right side. Three months later, BEV 10 mg/kg i.v. q14d was initiated, shortly interrupted for abdominal herniotomy in 2012, and continued for 3 years. Since 2014, concurrent low molecular weight heparin was given because of right lower limb deep venous thrombosis suspicion. Whereas GBM progression had not been detected for 2 years during anti- VEGF therapy, methionine PET MRI 6 months after BEV discontinuation revealed left temporal tumor recurrence. Rechallenge with BEV was initiated and the patient remained in stable clinical and radiographical condition for 10 months until now. This case highlights the utility of sequential BEV treatment in a patient being at high risk to develop chemotherapy-induced myelotoxicity. Long-term survival (< 3 years after diagnosis) in GBM has been attributed to patient-derived rather than tumor-derived factors. To our knowledge, this is the first description of effective long-term monotherapy with BEV for GBM and ongoing therapeutic response to single-agent BEV rechallenge in a patient with recurrent secondary GBM.