title: The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease.
abstract: BACKGROUND
  We compared the activity of denosumab with zoledronic acid for delaying or preventing hypercalcaemia of malignancy (HCM) in patients with advanced cancer and bone metastases or with multiple myeloma.
  
  
  METHODS
  Patient-level data were combined from two identically designed, randomised, double-blind, active-controlled, phase III trials of advanced cancer patients with breast cancer and other solid tumours (excluding breast or prostate cancer) or multiple myeloma. End-points included time to first on-study HCM, time to first and subsequent on-study HCM, proportion of patients experiencing HCM and proportion of patients experiencing recurrent HCM.
  
  
  RESULTS
  Denosumab significantly delayed the time to first on-study HCM, representing a 37% reduction in the hazard ratio (HR) compared with zoledronic acid (HR, 0.63; 95% confidence interval (CI): 0.41-0.98; P = 0.042) and reduced the risk of developing recurrent HCM (time to first and subsequent on-study HCM) by 52% (rate ratio, 0.48; 95% CI: 0.29-0.81; P = 0.006). The median time on study was 12.9 months. Fewer patients receiving denosumab compared with zoledronic acid experienced an HCM event (1.7% versus 2.7%; P = 0.028). Of the 84 patients experiencing an HCM event, 40% of those receiving zoledronic acid experienced >1 event of HCM compared with 31% of those receiving denosumab.
  
  
  CONCLUSIONS
  Denosumab treatment was more efficacious than treatment with zoledronic acid in delaying or preventing HCM in advanced cancer patients with breast cancer, other solid tumours or multiple myeloma.
authors.affiliation: Center for Gynecological Oncology, Mannheim, Germany. Electronic address: diel@spgo-mannheim.de.
authors.forename: Ingo J
authors.initials: IJ
authors.lastname: Diel
authors.affiliation: Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Body
authors.affiliation: Department of Internal Medicine, Stony Brook Cancer Center, NY, USA.
authors.forename: Alison T
authors.initials: AT
authors.lastname: Stopeck
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Saroj
authors.initials: S
authors.lastname: Vadhan-Raj
authors.affiliation: The Alfred Hospital, Prahran, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Steger
authors.affiliation: Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
authors.affiliation: Teaching Hospital Cochin, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Feng
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Ada
authors.initials: A
authors.lastname: Braun
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood* / Q000556:secondary*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000473:pathology; D009369:Neoplasms / Q000097:blood* / Q000473:pathology*; D016016:Proportional Hazards Models; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid
keywords: Breast cancer; Denosumab; Hypercalcaemia of malignancy; Multiple myeloma; Solid tumours; Supportive care; Zoledronic acid