Abstract TP445: Bevacizumab Therapy for Brain Arteriovenous Malformations

Introduction: Brain arteriovenous malformations (bAVM) are dynamic vascular malformations and a significant source of intracranial hemorrhage (ICH). Obliteration by interventional therapy is the only proven method to remove this hemorrhagic risk. Partial bAVM volume reduction using combination therapy does not lessen the risk of future ICH, though such adjuvant treatment is routinely practiced to permit definitive microsurgical resection or radiosurgery. High expression of vascular endothelial growth factor (VEGF) has been reported in bAVM and there is evidence for the beneficial effects of bevacizumab on AVMs from studies using the hereditary hemorrhagic telangiectasia (HHT) bAVM model and in liver AVMs in HHT patients. There is, however, no medical therapy approved to treat bAVMs. The goal of this study is to determine the beneficial effects of the anti-vascular endothelial growth factor drug, Bevacizumab, on bAVM. Hypothesis: Our hypothesis is that bAVM volume will decrease after 12 weeks of bevacizumab treatment. Additionally, we expect that bevacizumab treatment for bAVMs will not increase the occurrence of symptomatic ICH beyond that expected for natural history. Methods: The trial is a 10 patient one-armed, open-label study that will administer bevacizumab (5 mg/kg every 2 weeks) by IV infusion over the course of 12 weeks. The study will assess feasibility, safety, and preliminary evidence of efficacy in bAVMs deemed inoperable by current interventional means. For the purpose of estimating our effect size, we assumed that the bevacizumab treatment effect on bAVM volume will be proportional to the reduction of blood flow measured by the cardiac index in the hepatic AVM-bevacizumab trial. With a sample size of 10 paired observations and a one-tailed α =0.05, we have 84% power to detect a change in bAVM volume of 13%. We will compare pre- and post-treatment (26 weeks) volumes using a paired t-test. Significance: This study is the first medical intervention trial for bAVM. The study will meaningfully impact the clinical and research communities managing AVMs, regardless their anatomic location, and in turn those patients who suffer from them.