No survival improvement from bevacizumab for patients with newly diagnosed glioblastoma
Adding bevacizumab (Avastin) to standard chemotherapy and radiation treatment does not improve survival for patients with newly diagnosed glioblastoma, an often deadly brain cancer, researchers reported.
"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," said the study's senior author, Minesh P. Mehta, MB, ChB, of the University of Maryland School of Medicine and the University of Maryland Marlene and Stewart Greenebaum Cancer Center in Baltimore.
The US Food and Drug Administration 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 3 clinical trial, conducted by the Radiation Therapy Oncology Group (RTOG), randomized 637 patients at multiple centers into two groups.
Patients, who received the standard treatment, plus a placebo, had a median survival of 16.1 months compared with 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 prespecified criteria to be statistically meaningful, according to Mehta. The study was published in the New England Journal of Medicine (2014;370:699-708).
Mehta, who chairs the RTOG's brain tumor committee, said researchers also found an increase in symptoms among patients who took bevacizumab, compared with a placebo. "We observed higher rates of neurocognitive decline, increased symptom burden, and a decline in health-related quality of life over time among nonprogressing patients treated with bevacizumab," he said. Bevacizumab's side effects include vascular problems such as hypertension, protein in urine, and bleeding.
Mehta said 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 2 to 3 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 5 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).
Mehta noted 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 said.