In the trial, patients receiving Xgeva had a median time to bone metastases of 29.5 months, compared to 25.2 months for placebo patients. This 4.2-month improvement in median BMFS was statistically significant, and resulted in a hazard ratio of 0.85 (95% confidence interval, 0.73-0.98). Overall survival was similar between treatment arms; the effect on PFS was not statistically significant.
Study 20050147 was a randomized, double-blind, placebo-controlled multicenter study in men who had either a PSA level of at least 8 ng/mL or a PSA doubling time no greater than 10 months. Xgeva patients received 120 mg subcutaneously every 4 weeks. The primary end point was BMFS (defined as time to first occurrence of bone metastasis) or death from any cause. Secondary end points, tested sequentially if the previous end point was statistically significant, were time to first bone metastasis (symptomatic or asymptomatic) and overall survival. Metastases were monitored by imaging.
The rate of improvement is smaller than that proposed as sufficient evidence of benefit for a drug in nonmetastatic CRPC by some ODAC members at a September 2011 meeting, the FDA points out. During that panel session (which was a general discussion of prostate cancer treatments), Brent Logan, Ph.D., of the Medical College of Wisconsin, Milwaukee, suggested that benefit from a delay in bone metastasis depends on the length of the delay and a therapy’s toxicity.
Although the FDA voiced several concerns about the CPRC indication for Xgeva, the only voting question to ODAC is whether the biologic has "a favorable risk/benefit evaluation for the treatment of castrate-resistant prostate cancer at high risk for metastasis."
"The primary issue of this ODAC is whether BMFS of this magnitude represents clinical benefit, especially in context with the toxicities of therapy and the benefit already observed in patients diagnosed with bone metastases," the briefing materials note.
This coverage is provided courtesy of "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.