Adding bevacizumab (Avastin) to standard chemotherapy and radiation treatment does not improve survival for patients newly diagnosed with glioblastoma, a very aggressive form of brain cancer, researchers have found. The results of the large, multicenter study are being presented today during a plenary session at the American Society of Clinical Oncology (ASCO) annual meeting.
“Bevacizumab has been approved by the F.D.A. to treat recurrent glioblastoma. We asked, ‘Will adding bevacizumab to the standard of care significantly improve the outcome for newly diagnosed patients?’ ” says the study’s senior author, Minesh P. Mehta, MB, ChB, Professor, Department of Radiation Oncology, University of Maryland School of Medicine, and a radiation oncologist at the University of Maryland Marlene and Stewart Greenebaum Cancer Center. “Unfortunately, the answer was no. We didn’t see an improvement in overall survival or a statistically significant increase in progression-free survival.”
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. There was no clear benefit to giving the drug as a first-line treatment as opposed to later in the treatment process.
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.
A total of 637 patients were randomized into two groups as part of the Phase III clinical study, which was conducted by the Radiation Therapy Oncology Group (RTOG). The study was led by principal investigator Mark Gilbert, MD, a neuro-oncologist at The University of Texas MD Anderson Cancer Center, who is presenting the data at ASCO. Dr. Mehta is chair of the RTOG’s brain tumor committee.
Glioblastoma is the most common and deadliest of malignant primary brain tumors in adults. Standard treatment is surgery, followed by radiation therapy and chemotherapy with a drug called temozolomide. Even with treatment, the average survival is approximately only 16 months. 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).
According to Dr. Mehta, researchers are still analyzing the data to determine if patients with certain molecular markers may benefit from early treatment with bevacizumab. “We know this is a very heterogenous disease, and it is possible that there are subsets of patients that may show benefit, but not others. So performing the molecular analysis may be one way of extracting information which points to possible success,” he says.
E. Albert Reece, MD, PhD, MBA, 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, “Glioblastoma strikes two to three out of 100,000 people every year in the United States and Europe, and there remain few treatment options for patients. Despite these findings about the effectiveness of bevacizumab as an adjuvant for glioblastoma, large-scale clinical research studies such as this provide scientists with very valuable information in their quest to find possible new therapeutic approaches for this deadly cancer.”
During the course of the study, researchers also looked at factors such as patients’ symptom “burden” (the physical and emotional toll of cancer and its treatment), quality of life and cognitive abilities. They found that patients who had received bevacizumab when they were first diagnosed had greater symptom burden compared to those on standard therapy. Some of the patients in the standard therapy group were able to receive bevacizumab after they relapsed, so researchers were able to compare the effects of early versus later treatment. Bevacizumab’s side effects include vascular problems such as hypertension, protein in urine and bleeding.
“These ‘softer’ endpoints gave us very meaningful data,” Dr. Mehta says. “Although the primary end point, survival, is clearly a disappointment, the other lessons that we learned during the course of the trial are in fact very positive in terms of influencing the conduct of future trials in this disease.”