title: Clinical benefit in patients with metastatic bone disease: results of a phase 3 study of denosumab versus zoledronic acid.
abstract: BACKGROUND
  Patients with metastatic bone disease are living longer in the metastatic stage due to improvements in cancer therapy, making strategies to prevent the aggravation of bone disease and its complications, such as skeletal-related events (SREs) and pain, increasingly important.
  
  
  RESULTS
  In this phase 3 trial in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma, denosumab reduced the risk of radiation to bone by 22% relative to zoledronic acid (P = 0.026), prevented worsening of pain and pain interference (2-point increase in Brief Pain Inventory score; P < 0.05 versus zoledronic acid), and reduced the frequency of a shift from no/weak opioid analgesic use to strong opioids (P < 0.05 versus zoledronic acid at months 3-5). Denosumab delayed the time to moderate-to-severe pain compared with zoledronic acid in patients with mild or no pain at the baseline (P = 0.04), supporting early treatment. Health-related quality-of-life scores were similar in both groups. The number needed to treat to avoid one SRE for denosumab was 3 patient-years versus placebo and 10 patient-years versus zoledronic acid.
  
  
  CONCLUSIONS
  The use of denosumab was associated with better prevention of the complications of metastatic bone disease secondary to solid tumors or multiple myeloma versus zoledronic acid.
authors.affiliation: Division of Cancer Medicine, Department of Sarcoma Medical Oncology and Lymphoma/Myeloma, Section of Cytokines and Supportive Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: svadhanr@mdanderson.org.
authors.forename: S
authors.initials: S
authors.lastname: Vadhan-Raj
authors.affiliation: Department of Medical Oncology, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: von Moos
authors.affiliation: Sussex Health Outcomes Research & Education in Cancer (SHORE-C), University of Sussex, Brighton, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Fallowfield
authors.affiliation: Department of Health Services, School of Public Health, University of Washington, Seattle, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Patrick
authors.affiliation: Department of Medical Oncology, Paris Descartes University, AP-HP, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: C S
authors.initials: CS
authors.lastname: Cleeland
authors.affiliation: Department of Hematology-Oncology, Joan Karnell Cancer Center, Pennsylvania Hospital, Philadelphia, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Henry
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Novello
authors.affiliation: Department of Hematology, Irmandade da Santa Casa de Misericordia de São Paulo, São Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Hungria
authors.affiliation: Global Biostatistical Sciences, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Global Biostatistical Sciences, USA.
authors.forename: A
authors.initials: A
authors.lastname: Feng
authors.affiliation: Clinical Development, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Global Health Economics, Amgen Inc., Thousand Oaks, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chung
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D011788:Quality of Life; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D053245:RANK Ligand; D000069448:Denosumab; D000077211:Zoledronic Acid