title: Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid.
abstract: OBJECTIVE
  This analysis evaluated patient-reported outcomes and analgesic use in patients with bone metastases from solid tumours across three comparative studies of denosumab and zoledronic acid.
  
  
  METHODS
  Pooled data were analysed from three identically designed double-blind phase III studies comparing subcutaneous denosumab 120 mg with intravenous zoledronic acid 4 mg monthly in patients with bone metastases from breast cancer (n = 2,046), castration-resistant prostate cancer (n = 1,901) or other solid tumours (n = 1,597). Pain severity, pain interference, health-related quality of life and analgesic use were quantified.
  
  
  RESULTS
  At baseline, approximately half of patients had no/mild pain (53 % [1,386/2,620] denosumab; 50 % [1,297/2,578] zoledronic acid). Denosumab delayed onset of moderate/severe pain by 1.8 months (median, 6.5 vs 4.7 months; hazard ratio, 0.83; 95 % CI, 0.76-0.92; p < 0.001; 17 % risk reduction) and clinically meaningful increases in overall pain interference by 2.6 months (median, 10.3 vs 7.7 months; hazard ratio, 0.83; 95 % CI, 0.75-0.92; p < 0.001; 17 % risk reduction) compared with zoledronic acid. Strong opioid use and worsening of health-related quality of life were less common with denosumab.
  
  
  CONCLUSIONS
  Across three large studies of patients with advanced solid tumours and bone metastases, denosumab prevented progression of pain severity and pain interference more effectively than zoledronic acid.
authors: Kantonsspital Graubünden, Loëstrasse 170, 7000, Chur, Switzerland, Roger.vonmoos@ksgr.ch.
authors: Roger
authors: R
authors: von Moos
authors: Jean-Jacques
authors: JJ
authors: Body
authors: Blair
authors: B
authors: Egerdie
authors: Alison
authors: A
authors: Stopeck
authors: Janet E
authors: JE
authors: Brown
authors: Danail
authors: D
authors: Damyanov
authors: Lesley J
authors: LJ
authors: Fallowfield
authors: Gavin
authors: G
authors: Marx
authors: Charles S
authors: CS
authors: Cleeland
authors: Donald L
authors: DL
authors: Patrick
authors: Felipe G
authors: FG
authors: Palazzo
authors: Yi
authors: Y
authors: Qian
authors: Ada
authors: A
authors: Braun
authors: Karen
authors: K
authors: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010146:Pain / Q000517:prevention & control; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000473:pathology; D011788:Quality of Life; D055815:Young Adult; D000077211:Zoledronic Acid
chemical_list: D000700:Analgesics; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid
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