Aflibercept (VEGF-Trap) in High-Grade Gliomas
Pp. 171-175 (5)
Jan Drappatz, Andrew D. Norden and Patrick Y. Wen
Vascular endothelial growth factor (VEGF) is the key protein in the regulation of pathological
angiogenesis, a hallmark of glioblastomas. Inhibition of VEGF has become a major strategy in glioma therapy.
Most clinical trial data generated to date have been with bevacizumab, a humanized monoclonal antibody against
VEGF. Aflibercept (VEGF Trap; Regeneron, Inc.), is an engineered soluble receptor made from extracellular
domains of VEGFR1 and VEGFR2 which binds to all isoforms of VEGF and to placental growth factor (PlGF).
The avidity with which aflibercept binds to VEGF-A and VEGF-B is significantly higher than that for
bevacizumab. The toxicities observed include hypertension and proteinuria and are similar to those with other
therapies targeting the VEGF pathway. A phase II trial in patients with relapsed high-grade glioma demonstrated
encouraging activity. Ongoing trials are evaluating aflibercept in combination with temozolomide and radiation in
Department of Neurology, Division of Cancer Neurology, Brigham and Women’s Hospital.