Results from a recent clinical trial indicate that denosumab delayed the spread of prostate cancer metastases bones, however it did not prolong the lives of men.
Despite these findings, Dr. Matthew R. Smith, the lead investigator in the trial and a consultant to Amgen, said the results were meaningful because no drug before had been proved to prevent the spread of bone metastases (mets) in prostate cancer. This is significant because bone is a major cause of pain and disability in men with prostate cancer.
“This study is the first to demonstrate prevention of bone metastasis, the most devastating complication of prostate cancer,” Dr. Smith, an associate professor at Harvard Medical School and the Massachusetts General Hospital, said in an e-mail. “It addresses a critical unmet need.”
The trial involved 1,432 men with castrate resistant prostate cancer and without bone mets. The men were randomly assigned to receive denosumab every four weeks or a placebo. All subjects were considered to be a high risk for developing bone mets.
The goal was to see determine if denosumab could delay the time until either the cancer spread to the bone or the patient died from any cause. Denosumab delayed the median time for this to occur by 4.2 months, a statistically significant difference. Using a different statistic, the risk of bone metastasis or death was reduced 15 percent.
A major side effect experienced by the men taking denosumab was low calcium in their blood and the destruction of jaw bones (ONJ).
These results have not yet been peer reviewed
The benefit came entirely from delaying bone metastasis, not death. Dr. Roger M. Perlmutter, executive vice president for research and development at Amgen, said the trial had not been expected to show a survival benefit since most of the patients lived through the course of the trial. Also, men who experienced bone metastasis were removed from the study so they could be treated with a drug that helps prevent fractures.
Denosumab works by blocking a protein involved in the bone destruction. That presumably makes the bone a less hospitable environment for cancer cells to take root.
The drug, sold under the name Xgeva, was approved by the FDA in November to help prevent fractures and other skeletal problems after prostate and other cancers had already spread to the bone. The drug is also sold to treat osteoporosis under the name Prolia.
Joel T. Nowak, M.A., M.S.W.