Biomarkers predict brain tumor therapy response
A report published June 23 in Cancer Research highlights a new biomarker that may be useful in identifying patients with recurrent glioblastoma who would respond better to anti-vascular endothelial growth factor therapy, specifically cediranib.
Cediranib, an investigational, oral agent that is administered once daily, is a highly potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Using a form of MRI that looked at the mechanism of action of this agent, the researchers were able to determine, even as early as after a single dose of cediranib, those patients who benefited from the agent and those who did not.
"We found that results from an advanced MRI scan taken just a day after starting treatment correlated with survival. Combining MRI with blood biomarkers did an even better job of identifying patients who best responded to treatment," said researcher A. Gregory Sorensen, M.D., associate professor of radiology and health sciences and technology at Harvard Medical School, Massachusetts General Hospital in Boston. "If this approach is validated in larger studies, we could use these tools to keep patients on therapies that their tumors respond to, and shift non-responders to other therapies much earlier."
Sorensen and colleagues sought to find the potential biomarkers that could be used to predict those patients who would respond better from anti-angiogenic therapy early in the course of treatment by use of MRI.
The researchers measured vascular normalization prior to and one day after patients' received cediranib using an advanced MRI technique. They performed blood analysis and examined correlations between vascular parameters and treatment response after a single dose of cediranib in 31 patients with recurrent glioblastoma; all biomarkers were measured in 28 patients.
The correlative analysis in this single arm, phase II study showed that those patients whose extent of vascular normalization was greater, had a longer duration of overall survival as well as progression-free survival, according to the study's authors. Median overall survival rate was 227 days; some patients lived for about two years and some lived less than two months.
The researchers said that these findings need to be validated in larger, prospective studies. They are currently conducting several studies based on these results in efforts to evaluate the benefits and prolonged survival of these patients.
"We hope to develop biomarkers to help physicians and researchers know if a patient is responding; if they are not responding we can move them to a more effective therapy, if they are responding we can continue treatment, even if the treatment carries risks or side effects," Sorensen said.
Cediranib, an investigational, oral agent that is administered once daily, is a highly potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Using a form of MRI that looked at the mechanism of action of this agent, the researchers were able to determine, even as early as after a single dose of cediranib, those patients who benefited from the agent and those who did not.
"We found that results from an advanced MRI scan taken just a day after starting treatment correlated with survival. Combining MRI with blood biomarkers did an even better job of identifying patients who best responded to treatment," said researcher A. Gregory Sorensen, M.D., associate professor of radiology and health sciences and technology at Harvard Medical School, Massachusetts General Hospital in Boston. "If this approach is validated in larger studies, we could use these tools to keep patients on therapies that their tumors respond to, and shift non-responders to other therapies much earlier."
Sorensen and colleagues sought to find the potential biomarkers that could be used to predict those patients who would respond better from anti-angiogenic therapy early in the course of treatment by use of MRI.
The researchers measured vascular normalization prior to and one day after patients' received cediranib using an advanced MRI technique. They performed blood analysis and examined correlations between vascular parameters and treatment response after a single dose of cediranib in 31 patients with recurrent glioblastoma; all biomarkers were measured in 28 patients.
The correlative analysis in this single arm, phase II study showed that those patients whose extent of vascular normalization was greater, had a longer duration of overall survival as well as progression-free survival, according to the study's authors. Median overall survival rate was 227 days; some patients lived for about two years and some lived less than two months.
The researchers said that these findings need to be validated in larger, prospective studies. They are currently conducting several studies based on these results in efforts to evaluate the benefits and prolonged survival of these patients.
"We hope to develop biomarkers to help physicians and researchers know if a patient is responding; if they are not responding we can move them to a more effective therapy, if they are responding we can continue treatment, even if the treatment carries risks or side effects," Sorensen said.