Prior to the formal review, the FDA has raised questions about the ultimate approval of Amgen’s Xgeva (denosumab) for men with metastatic, advanced prostate cancer who have not yet developed metastasized to the bone. Xgeva has been shown to delay tumors spreading to bones, but it does not extend life, the holy grail of the FDA.

The FDA will be holding on February 8 an advisory panel that will meet to recommend whether to expand Xgeva’s use (currently it is approved for men who have developed bone metastasizes) to include men with advanced prostate cancer who have not yet developed bone mets.

FYI- Xgeva is also Known as Prolia for the treatment of osteoporosis in menopausal women, it was approved by the FDA November of 2010.

According to a published study in November in The Lancet men who took Xgeva experienced bone metastases 4.2 months later on average than those that took a placebo. However, survival didn’t differ between the groups.

If approved, Xgeva would be for men who are castrate resistant and whose cancer hasn’t spread to the bone.

In the clinical trial of 1,432 men, five percent developed osteonecrosis of the jaw, which can cause jaw pain, tooth infection and bone inflammation, according to The Lancet study. Bone metastases are one of the most common causes of pain in men with advanced prostate cancer. In the trial some men experienced as much as a 7.5-month delay in developing bone metastases.

The big question is will the FDA approve it without demonstrating any survival advantage? “I would not be surprised if this doesn’t get approved,” said Bill Tanner, an analyst at Lazard Capital Markets in New York.” However in September the panel also met to discuss the testing drugs for prostate cancer patients who are castrate resistant and whose cancer hasn’t spread to the bones. The problem that might mean the failure to get the approval comes from the oncologists on the panel who considered a two-year bone metastases delay beneficial while one year and six months was considered questionable.

The panel consists of nine oncologists and a bio-statistician. The FDA does not have to follow the panel’s recommendation.
The FDA is scheduled to make a decision by April 26.

My opinion – Since bone metastases can be so painful, even a 4.2 month delay (again, this is the medium, so one half of men taking Xgeva will have an even longer delay to developing painful bone metastases) to experiencing what can become intractable pain seems to be a real value making Xgeva worthy of FDA approval.

Joel T. Nowak, M.A., M.S.W.