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The future of antiangiogenic treatment in glioblastoma
Oliver L Chinot1, David A Reardon
1aAP-HM, Pole Neuroscience Cliniques, Service de Neuro-Oncologie, CHU Timone, Aix-Marseille University, Marseille, France bDepartment of Medical Oncology, Center for Neuro-Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Purpose Of Review:
A major recent clinical research focus for glioblastoma has been the therapeutic evaluation of antiangiogenic agents. Several vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors and a soluble decoy VEGF receptor have demonstrated nominal benefit among patients. In contrast, bevacizumab, a humanized VEGF monoclonal antibody, exhibits evidence of apparent antitumor benefit, although these data remain controversial. In this review, we summarize how results of clinical trials evaluating bevacizumab to date influence the future of this therapeutic for recurrent and newly diagnosed glioblastoma patients.
Recent Findings:
Recently reported, placebo-controlled phase III studies demonstrate a meaningful progression-free survival increment, but no overall survival benefit among newly diagnosed patients treated with bevacizumab. For unclear reasons, quality-of-life surveys from these studies revealed divergent results. Among recurrent patients, uncontrolled trials demonstrate improved overall radiographic response and progression-free survival rates, although the impact of bevacizumab on overall survival remains to be defined by an ongoing randomized phase III trial.
Summary:
The role of bevacizumab for glioblastoma remains uncertain but will likely be strongly influenced by results of a randomized phase III study among recurrent patients as well as further investigation of gene expression biomarker profiles to identify newly diagnosed patients more likely to derive survival benefit.
Insights
Bevacizumab shows progression-free survival benefits for glioblastoma patients but not overall survival. Further research is needed to clarify its role and identify patient subgroups who may benefit most from this vascular endothelial growth factor antibody.
Area of Science:
- Neuro-oncology
- Cancer therapy
- Clinical research
Background:
- Antiangiogenic agents are a key focus for glioblastoma treatment.
- Vascular endothelial growth factor (VEGF) inhibitors have shown limited success.
- Bevacizumab, a VEGF monoclonal antibody, has controversial antitumor benefit data.
Purpose of the Study:
- To review clinical trial data on bevacizumab for glioblastoma.
- To assess the influence of current data on future therapeutic strategies.
- To evaluate bevacizumab's role in newly diagnosed and recurrent glioblastoma.
Main Methods:
- Review of recent clinical trials evaluating bevacizumab.
- Analysis of placebo-controlled phase III studies for newly diagnosed patients.
- Examination of uncontrolled trials for recurrent glioblastoma patients.
Main Results:
- Bevacizumab improved progression-free survival but not overall survival in newly diagnosed patients.
- Quality-of-life results were divergent in newly diagnosed patients.
- Recurrent glioblastoma patients showed improved radiographic response and progression-free survival, but overall survival impact is pending.
Conclusions:
- The role of bevacizumab in glioblastoma remains uncertain.
- Results from a randomized phase III trial in recurrent glioblastoma are anticipated.
- Biomarker research is crucial to identify patients likely to benefit from bevacizumab.
