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ASCO 2013: Adding Bevacizumab to Standard First-line Chemoradiation for Glioblastoma Does Not Improve Overall Survival

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Key Points

  • A randomized phase III study found no improvement in overall survival after the addition of bevacizumab to standard first-line chemoradiation for glioblastoma.
  • Patients who received bevacizumab also experienced more side effects, including hypertension, venous thromboembolism/pulmonary embolism, wound healing issues, gastrointestinal perforation, hemorrhage, and neutropenia.
  • The findings suggest that bevacizumab should not be a part of first-line therapy for patients with glioblastoma.

A randomized phase III study found no improvement in overall survival after the addition of bevacizumab (Avastin) to standard first-line chemoradiation for glioblastoma. Patients who received bevacizumab also experienced more side effects compared to those treated with chemoradiation alone. The study was presented at the 2013 ASCO Annual Meeting (Abstract 1) by Mark R. Gilbert, MD, Professor of Neuro-oncology at The University of Texas MD Anderson Cancer Center in Houston.

“One of the most prominent features of gliomblastoma is angiogenesis,” Dr. Gilbert said,  which made it seem like a logical target for bevacizumab, an antibody that blocks the growth of tumor blood vessels. Bevacizumab is currently approved by the Food and Drug Administration (FDA) for patients with recurrent glioblastoma and has been used off-label as first-line therapy in certain patients. The new findings, however, suggest that bevacizumab should not be a part of first-line therapy for patients with glioblastoma.

“Unless we can identify a group of patients that clearly benefits from early use of bevacizumab, it appears that it should not be used in the first-line setting,” Dr. Gilbert stated. “Bevacizumab remains an important part of our armory against glioblastoma, but in most situations it should be reserved as a salvage regimen.”

Slight Improvement in Progression-free Survival

In this multi-institutional clinical trial, 637 patients with newly diagnosed glioblastoma were randomly assigned to treatment with chemoradiation (temozolomide and radiation) plus placebo or chemoradiation plus bevacizumab. All patients had surgery prior to starting chemoradiation. Patients were allowed to cross over to the placebo group or continue bevacizumab at the time of progression.

The median overall survival was not statistically different between the two groups—15.7 months with bevacizumab vs 16.1 months with placebo. The median progression-free survival was longer in the bevacizumab group relative to the placebo group—10.7 months vs 7.3 months—but “even though the P value was .007, it did not reach our predetermined level of success,” Dr. Gilbert said. A subgroup analysis based on molecular markers (MGMT methylation status and a nine-gene expression signature) found no subgroup with improved survival using bevacizumab.

More Side Effects with Bevacizumab

Overall, there were more side effects in the bevacizumab group. These included hypertension, venous thromboembolism/pulmonary embolism, wound healing issues, gastrointestinal perforation, hemorrhage, and neutropenia. However, Dr. Gilbert said that toxicity differences alone would not have precluded the decision to use bevacizumab had the trial found a survival benefit.

Patients in the bevacizumab arm had a greater increase of symptom burden and more decline of neurocognitive function over time compared to patients in the placebo arm. Molecular profiles of tumor samples collected on this study, as well as imaging scans, are being examined to determine if there is any group of patients that could still benefit from bevacizumab in the first-line setting.

This research was supported in part by the National Cancer Institute and Genentech. Dr. Gilbert reported a consultant or advisory role with Novartis, EMD Serono, Genentech, and Merck; honoraria from Novartis, EMD Serono, Genentech, and Merck; and research funding from GlaxoSmithKline, Genentech, and Merck.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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