Glioblastoma: Avastin Did Not Improve Survival or Symptoms

Minesh P. Mehta, M.B., Ch.B. F.A.S.T.R.O. Professor of Radiation Oncology, University of Maryland School of Medicine Radiation oncologist, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Chair, RTOG brain tumor Interview with:
Minesh P. Mehta, M.B., Ch.B. F.A.S.T.R.O.
Professor of Radiation Oncology,
University of Maryland School of Medicine
Radiation oncologist, University of Maryland Marlene and Stewart Greenebaum Cancer Center What are the main findings of the study?

Dr. Mehta: RTOG 0825 was a clinical trial evaluating whether the addition of a novel drug that inhibits tumor vascular growth, bevacizumab, to the standard of care for glioblastoma, an aggressive brain tumor, would prolong survival. Patients were allocated randomly to one of two different treatment regimens – the standard of care, which includes radiotherapy and a drug known as temozolomide, or another regimen of radiation, temozolomide and bevacizumab. The trial design was double-blinded, and therefore, on one arm patients received the bevacizumab, whereas on the other arm they received a placebo. The survival on both arms was equivalent, and therefore it was fairly concluded that bevacizumab failed to prolong survival when given initially as part of treatment for glioblastoma.

Freedom from progression, referred to as progression-free survival was also measured on this trial, and although bevacizumab appeared to lengthen progression-free survival, this level of benefit did not meet the pre-defined goals, and is therefore regarded as statistically not demonstrating an improvement.

Additional endpoints included outcomes reported by the patient, including the burden of symptoms, and the impact of these on the quality of life, as well as effects on the brain, known as neurocognitive changes. Bevacizumab did not improve these endpoints either. Were any of the findings unexpected?

Dr. Mehta: This trial was based on an earlier trial in which patients with recurrent glioblastoma were treated with bevacizumab. In that trial, progression of disease was delayed, and tumor shrinkage on brain MRI scans was noted, resulting in FDA approval for use in recurrent glioblastoma. Based on those results, as well as the known biology of this tumor, there was good expectation that a survival benefit would be observed. Failure to observe that was somewhat unexpected and truly disappointing. What should clinicians and patients take away from your report?

Dr. Mehta: This agent bevacizumab is known to help several patients with recurrent glioblastoma, and the results of this trial should not detract from that; patients and physicians need to keep this in mind and recognize that the drug has value in the recurrent setting. Upfront use cannot be supported in terms of improving duration of survival. What recommendations do you have for future research as a result of this study?

Dr. Mehta: improved, but in that trial, the patient-reported outcomes were more favorable for the bevacizumab arm. Therefore, the collective data from both trials regarding these endpoints are expected to be analyzed in greater detail. Further, it is possible that certain subsets of patients might have benefited from the agent, and specific molecular evaluation of individual patients’ tumors is ongoing to tease this out.


A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma

Mark R. Gilbert, M.D., James J. Dignam, Ph.D., Terri S. Armstrong, Ph.D., A.N.P.-B.C., Jeffrey S. Wefel, Ph.D., Deborah T. Blumenthal, M.D., Michael A. Vogelbaum, M.D., Ph.D., Howard Colman, M.D., Ph.D., Arnab Chakravarti, M.D., Stephanie Pugh, Ph.D., Minhee Won, M.A., Robert Jeraj, Ph.D., Paul D. Brown, M.D., Kurt A. Jaeckle, M.D., David Schiff, M.D., Volker W. Stieber, M.D., David G. Brachman, M.D., Maria Werner-Wasik, M.D., Ivo W. Tremont-Lukats, M.D., Erik P. Sulman, M.D., Kenneth D. Aldape, M.D., Walter J. Curran, Jr., M.D., and Minesh P. Mehta, M.D.

N Engl J Med 2014; 370:699-708
February 20, 2014DOI: 10.1056/NEJMoa1308573

Last Updated on February 22, 2014 by Marie Benz MD FAAD