Amgen (Nasdaq: AMGN) today announced that a pivotal, Phase 3, head-to-head trial evaluating denosumab versus Zometa® (zoledronic acid) in the treatment of bone metastases in 1,901 men with advanced prostate cancer met its primary and secondary endpoints. Denosumab demonstrated superiority over Zometa for both delaying the time to the first on-study skeletal related event (SRE) (fracture, radiation to bone, surgery to bone or spinal cord compression) (hazard ratio 0.82, 95 percent CI: 0.71, 0.95), and reducing the rate of multiple SREs (hazard ratio 0.82, 95 percent CI: 0.71, 0.94). Both results were statistically significant.
Overall rates of adverse events and serious adverse events, including infections, were generally similar between the two arms. Osteonecrosis of the jaw was infrequent (22 patients receiving denosumab as compared with 12 patients receiving Zometa) and there was no statistically significant difference between treatment arms. As with previous studies in advanced cancer patients, hypocalcemia was more frequent in the denosumab arm. Both overall survival and the time to cancer progression were balanced between treatment arms.
"These Phase 3 results demonstrate the ability of denosumab to delay bony complications in patients suffering from metastatic prostate cancer," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "Denosumab has shown remarkable consistency in reducing the serious complications of bone metastases. Today's results greatly enhance our understanding of the efficacy of denosumab in multiple different tumor types."
This study is the final of three pivotal trials in a total of over 5,700 advanced cancer patients investigating the potential of denosumab to treat bone metastases. Results from the previous two trials were presented in September 2009. These three studies will form the basis of the clinical evidence package for denosumab in advanced cancer, which will be submitted to regulatory authorities later this year.
Full efficacy and safety data for the prostate cancer study will be submitted to the American Society for Clinical Oncology, for possible presentation at their meeting in early June. Additionally, results are expected in the second half of the year from a study investigating whether denosumab may prolong bone metastasis-free survival in prostate cancer patients.