Denosumab Demonstrated Superiority Over Zometa in Delay of Complications Due to Bone Metastases in Advanced Prostate Cancer
Amgen announced detailed results from a Phase 3, head-to-head trial which compared the efficacy and safety of denosumab versus Zometa(R) (zoledronic acid) in 1,901 patients with hormone-refractory prostate cancer and bone metastases. The study met its primary and secondary endpoints and demonstrated denosumab's superiority over Zometa in delaying or preventing skeletal related events (SREs).
In patients with skeletal metastases, the growing cancer cells weaken and destroy the bone around the tumor. This can result in a number of serious complications, collectively called SREs, comprising fracture, radiation to bone, surgery to bone or spinal cord compression. All can be serious complications for advanced cancer patients.
In this study, denosumab was superior to Zometa in significantly delaying the time to first on-study SRE (hazard ratio 0.82; 95 percent CI: 0.71, 0.95; P = 0.008) with a median time to first on-study SRE of 20.7 months versus 17.1 months for Zometa. Denosumab was also superior to Zometa in significantly delaying the development of multiple SREs (time to first and subsequent on-study SRE) (hazard ratio 0.82; 95 percent CI: 0.71, 0.94; P = 0.004).
Overall rates of adverse events (AEs) and serious adverse events, including infections, were generally similar between the two arms. Osteonecrosis of the jaw (ONJ) was infrequent (22 patients receiving denosumab (2.3 percent) as compared with 12 patients receiving Zometa (1.3 percent)); the incidence of ONJ was not significantly different between treatment arms. As with previous studies in advanced cancer patients, hypocalcemia was more frequent in the denosumab arm. Both overall survival (hazard ratio 1.03; 95 percent CI: 0.91, 1.17; P=0.65) and the time to cancer progression (hazard ratio 1.06; 95 percent CI: 0.95, 1.18; P=0.30) were balanced between treatment arms. The most common AEs for denosumab were anemia, back pain, and nausea, and the most common AEs for Zometa were anemia, back pain, and decreased appetite.
This study is the final of three pivotal trials involving over 5,700 advanced cancer patients that explored the potential of denosumab to treat bone metastases. These three studies form the basis of the clinical evidence package for denosumab in advanced cancer, and were submitted to regulatory authorities in the United States (U.S.) and in the European Union (EU).
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