Alison Stopeck1, Allan Lipton1, Jean-Jacques Body1, Guenther G. Steger1, Katia Tonkin1, Richard H. De Boer1, Mikhail Lichinitser1, Yasuhiro Fujiwara1, Denise A. Yardley1, María Eugenia Ibarrarán Viniegra1, Michelle Fan1, Qi Jiang1, Roger Dansey1, Susie Jun1, Ada Braun1
1From the University of Arizona, Arizona Cancer Center, Tucson, AZ; Penn State Milton S. Hershey Medical Center, Hershey, PA; Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels, Belgium; Medical University of Vienna, Vienna, Austria; Cross Cancer Institute, Edmonton, Alberta, Canada; Western and Royal Melbourne Hospitals, Melbourne, Victoria, Australia; Blokhin Cancer Research Center, Moscow, Russia; National Cancer Center Hospital, Tokyo, Japan; Sarah Cannon Research...
Tóm tắt
Purpose This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39). Conclusion Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.
