Adding bevacizumab (Avastin) to standard chemotherapy and radiation treatment does not improve survival for patients newly diagnosed with the often deadly brain cancer glioblastoma, researchers report in the Feb. 20 issue of the New England Journal of Medicine.
"We didn't see an improvement in overall survival or a statistically significant increase in progression-free survival, as defined in the context of this trial," says the study's senior author, Minesh P. Mehta, M.B., Ch.B., Professor of Radiation Oncology at the University of Maryland School of Medicine and a radiation oncologist at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.
The U.S. Food and Drug Administration (FDA) has approved the use of bevacizumab to treat recurrent glioblastoma. Researchers sought to learn whether the drug could be beneficial as a first-line treatment.
The Phase III clinical trial, conducted by the Radiation Therapy Oncology Group (RTOG), randomized 637 patients at multiple centers, including the University of Maryland Greenebaum Cancer Center, into two groups.
Patients who received the standard treatment, plus a placebo, had a median survival of 16.1 months compared to 15.7 months for those who received the standard treatment plus bevacizumab. Although it took slightly longer for the cancer to progress in patients receiving bevacizumab (10.7 months vs. 7.3 months), the rate of progression-free survival did not meet pre-specified criteria to be statistically meaningful, according to Dr. Mehta.
Dr. Mehta, who chairs the RTOG's brain tumor committee, says researchers also found an increase in symptoms among patients who took bevacizumab, compared to a placebo. "We observed higher rates of neurocognitive decline, increased symptom burden and a decline in health-related quality of life over time among non-progressing patients treated with bevacizumab," he says. Bevacizumab's side effects include vascular problems such as hypertension, protein in urine and bleeding.
Dr. Mehta says the cognitive decline may have stemmed from unrecognized progression of the cancer, masked by the use of bevacizumab, or neurotoxicity related to the bevacizumab.
Glioblastoma is the most common and deadliest of malignant primary brain tumors in adults. It strikes two to three out of 100,000 people every year in the United States and Europe. Standard treatment is surgery, followed by radiation therapy and chemotherapy with temozolomide. Even with treatment, the average survival is approximately only 16 months. Few patients survive beyond five years. This cancer is characterized by the growth of new blood vessels, known as angiogenesis. Bevacizumab, a monoclonal antibody, is an angiogenesis inhibitor that targets a chemical signal, vascular endothelial growth factor A (VEGF-A).
The study, which was led by principal investigator Mark Gilbert, M.D., a neuro-oncologist at The University of Texas M.D. Anderson Cancer Center, was sponsored by the National Cancer Institute (NCI) (U10 CA21661 and U10 CA37422). Genentech provided additional support through an educational grant.
E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine, says, "Although researchers found that bevacizumab did not improve survival for patients newly diagnosed with glioblastoma, large-scale clinical studies such as this provide scientists with very valuable information and lay the groundwork for future research. Patients with glioblastoma have very few treatment options, and we need to continue our search for new ways to attack this very aggressive cancer."
Dr. Mehta notes that angiogenesis inhibitors, such as bevacizumab, have shown great promise in the treatment of cancer, but this study offers some perspective. "Anti-angiogenic agents are not going to be a cure-all for every cancer. They will probably have a role in several malignancies but not necessarily every one," he says.
- Mark R. Gilbert, James J. Dignam, Terri S. Armstrong, Jeffrey S. Wefel, Deborah T. Blumenthal, Michael A. Vogelbaum, Howard Colman, Arnab Chakravarti, Stephanie Pugh, Minhee Won, Robert Jeraj, Paul D. Brown, Kurt A. Jaeckle, David Schiff, Volker W. Stieber, David G. Brachman, Maria Werner-Wasik, Ivo W. Tremont-Lukats, Erik P. Sulman, Kenneth D. Aldape, Walter J. Curran, Minesh P. Mehta. A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma. New England Journal of Medicine, 2014; 370 (8): 699 DOI: 10.1056/NEJMoa1308573
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