TRIP

Bone Drug Slows Mets in Aggressive Prostate Ca

MedPageToday, 2012

Clinical practitioners should take note, Adam Kibel, MD, of Brigham and Women's Hospital in Boston, commented from the audience.
"Historically you might have thought men at lower risk would be more likely to benefit because they would be easier to treat," session moderator Robert Reiter, MD, of the University of California Los Angeles, agreed in an interview with MedPage Today .
Yet this finding also has implications for use in less aggressive prostate cancer cases, Kibel pointed out.
"As we contemplate moving all of these treatments into earlier stages disease, it's important to understand whether the less aggressive cancer patients benefit," he added.
The rationale is clearly strongest for the higher risk cases, who develop most of the bone metastases, but the study didn't include many lower risk patients and thus couldn't answer the absolute benefit in those cases, Smith acknowledged.
The denosumab study was the first to show a benefit in preventing first bone metastases in prostate cancer patients, whereas bone drugs had previously been proven only in a population with existing metastases, Reiter explained.
They were considered high risk due to a PSA of at least 8 ng/mL (average 12 ng/mL) or a doubling time of 10 months or less (average five months) who were randomized to calcium and vitamin D supplements plus either 120 mg subcutaneous denosumab every four weeks or placebo.
The subanalysis in only those men with more aggressive PSA characteristics, reflected by a doubling time of 10 months or less, turned up a 16% lower risk of bone metastasis or death with denosumab compared with placebo ( P =0.042), prolonging metastasis-free survival by about six months.
In the group with a PSA doubling time of four months or less, denosumab decreased risk by 29% compared with placebo ( P =0.004).
As expected from prior studies with denosumab, the drug was associated with more hypocalcemia (1.7% versus 0.3% with placebo) as well as a 5% rate of osteonecrosis of the jaw (ONJ), which didn't occur in the control group.
It's the major driver of morbidity for the disease and I believe the results support a favorable benefit-to-risk profile."