Bevacizumab in high-grade gliomas: past, present, and future

Abstract

The survival of patients with high-grade gliomas (anaplastic gliomas and glioblastoma) remains poor despite current treatment modalities. However, an enhanced understanding of gliomagenesis is supporting the development of targeted molecular therapies with the potential for improving clinical outcomes. Glioblastoma (GBM) is characterized by extensive microvascular proliferation and the production of large amounts of VEGF. Bevacizumab is a humanized IgG1 monoclonal antibody that selectively binds with high affinity to human VEGF and neutralizes VEGF’s biologic activity. Preclinical data indicate that angiogenesis is essential for the proliferation and survival of GBM cells. A number of studies have evaluated the outcomes of both newly diagnosed and recurrent GBM patients with bevacizumab in a prospective manner. Here, we discuss the role of bevacizumab in the treatment of anaplastic gliomas and GBM in the recurrent and upfront setting.

Keywords:

• angiogenesis
• bevacizumab
• chemotherapy
• high-grade glioma
• newly diagnosed

Financial & competing interests disclosure

MS Ahluwalia serves on the Genentech advisory board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Glioblastoma (GBM) is an aggressive malignant brain tumor characterized by extensive microvascular proliferation and increased production of VEGF.

• Bevacizumab (a humanized IgG1 monoclonal antibody) was FDA approved in 2009 for the treatment of recurrent GBM due to an increase in overall response rate.

• Numerous clinical trials have not shown any improvement in overall survival (OS) when chemotherapy is combined with bevacizumab versus bevacizumab alone in the recurrent GBM setting with the exception of BELOB trial.

• AVAglio and RTOG 0825, two large randomized Phase III trials failed to show an improvement in OS in the newly diagnosed GBM with bevacizumab in addition to standard of care chemotherapy and radiation.

• AVAglio study showed a statistical significant improvement in progression free survival.

• Number of clinical trials of bevacizumab in combination with other therapeutic modalities such as targeted therapies, radiosurgery are ongoing.