title: Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics.
abstract: BACKGROUND
  Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics.
  
  
  METHODS
  Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type.
  
  
  RESULTS
  Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types.
  
  
  CONCLUSIONS
  Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level.
authors.affiliation: Division of Oncology, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, USA. Electronic address: alipton@hmc.psu.edu.
authors.forename: A
authors.initials: A
authors.lastname: Lipton
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Stony Brook Cancer Center, Stony Brook, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Stopeck
authors.affiliation: Joan Karnell Cancer Center at Pennsylvania Hospital, Philadelphia, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Henry
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Carolina Urologic Research Center, Myrtle Beach, USA.
authors.forename: N
authors.initials: N
authors.lastname: Shore
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.affiliation: Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vadhan-Raj
authors.affiliation: Academic Unit of Clinical Oncology, University of Sheffield, Weston Park Hospital, Sheffield, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Brown
authors.affiliation: Cabrini Medical Centre, Melbourne, Australia.
authors.forename: G E
authors.initials: GE
authors.lastname: Richardson
authors.affiliation: Departments of Surgery and Urology, University of Montreal Hospital Center, Montreal, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Saad
authors.affiliation: Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Yardley
authors.affiliation: Hematology/Oncology, Amgen Inc., Thousand Oaks, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Hematology/Oncology, Amgen Inc., Thousand Oaks, USA.
authors.forename: A
authors.initials: A
authors.lastname: Balakumaran
authors.affiliation: Hematology/Oncology, Amgen Inc., Thousand Oaks, USA.
authors.forename: A
authors.initials: A
authors.lastname: Braun
mesh_terms: D000279:Administration, Cutaneous; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001847:Bone Diseases / Q000517:prevention & control; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000069448:Denosumab / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid
keywords: Bone metastases; Denosumab; Skeletal-related event; Subgroup; Zoledronic acid