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Updated: May 24, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Is there a world beyond bevacizumab in targeting angiogenesis in glioblastoma?
Katharina Seystahl1, Michael Weller
1University Hospital Zurich, Department of Neurology, Frauenklinikstrasse 26, Zurich, Switzerland.
Introduction:
Antiangiogenic approaches are currently the dominating experimental therapeutic strategy in glioblastoma. First enthusiasm was provoked by promising radiological response rates and an apparent clinical benefit with some of these agents. Major limitations include the modest number of durable responses, the lack of cytotoxic antitumor activity, of synergy when combined with chemotherapy and of an overall survival benefit.
Areas Covered:
We review the rationale as well as preclinical and clinical evidence for the future development of antiangiogenic agents in glioblastoma. The most prominent approach targets VEGF and includes agents such as the VEGF antibody bevacizumab, the VEGF receptor fusion protein aflibercept or the tyrosine kinase inhibitors cediranib and XL-184. Inhibition of angiogenic pathways by small molecules, for example, enzastaurin, or anti-integrin-based approaches, for example, cilengitide, represent alternative strategies.
Expert Opinion:
Enzastaurin and cediranib failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in Phase II. By contrast, bevacizumab was conditionally approved in many countries. Recently completed Phase III trials for bevacizumab and cilengitide in the first-line setting will define the future role of these agents. This intense clinical trial activity reflects the hope that antiangiogenic agents will become part of the limited therapeutic options for glioblastoma.
Insights
Antiangiogenic therapies show limited durable responses and survival benefits in glioblastoma. Despite some approvals like bevacizumab, further trials are needed to define the role of these agents in brain tumor treatment.
Area of Science:
- Neuro-oncology
- Cancer Therapeutics
- Angiogenesis Inhibition
Background:
- Antiangiogenic therapies are a primary experimental strategy for glioblastoma.
- Initial enthusiasm for agents targeting vascular endothelial growth factor (VEGF) has waned due to limitations.
- These limitations include modest durable responses, lack of cytotoxic activity, and no proven overall survival benefit.
Purpose of the Study:
- To review the rationale, preclinical, and clinical evidence for antiangiogenic agents in glioblastoma.
- To evaluate the efficacy and future potential of various antiangiogenic strategies.
- To discuss the current status and future directions of antiangiogenic therapy in glioblastoma treatment.
Main Methods:
- Review of preclinical and clinical data on antiangiogenic agents.
- Focus on agents targeting VEGF, including bevacizumab, aflibercept, cediranib, and XL-184.
- Consideration of alternative strategies like small molecule inhibitors (enzastaurin) and anti-integrin approaches (cilengitide).
Main Results:
- Enzastaurin, cediranib, and aflibercept have failed in recent clinical trials for glioblastoma.
- Bevacizumab received conditional approval in several countries.
- Ongoing Phase III trials for bevacizumab and cilengitide in first-line glioblastoma will be critical.
Conclusions:
- Antiangiogenic agents have shown mixed results in glioblastoma treatment.
- Bevacizumab remains conditionally approved, with ongoing trials to determine its definitive role.
- The future of antiangiogenic therapy in glioblastoma depends on the outcomes of current and future clinical investigations.
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