title: Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid.
abstract: BACKGROUND
  In this study, the authors evaluated the effect of denosumab versus zoledronic acid (ZA) on pain in patients with advanced breast cancer and bone metastases.
  
  
  METHODS
  The prevention of pain, reduction in pain interference with daily life activities, and the proportion of patients requiring strong opioid analgesics were assessed in a randomized, double-blind, double-dummy phase 3 study comparing denosumab with ZA for preventing skeletal-related events in 2046 patients who had breast cancer and bone metastases. Patients completed the Brief Pain Inventory-Short Form at baseline and monthly thereafter.
  
  
  RESULTS
  Fewer patients who received denosumab reported a clinically meaningful worsening of pain severity (≥2-point increase) from baseline compared with patients who received ZA, and a trend was observed toward delayed time to pain worsening with denosumab versus ZA (denosumab, 8.5 months; ZA, 7.4 months; P = .08). In patients who had no/mild pain at baseline, a 4-month delay in progression to moderate/severe pain was observed with denosumab compared with ZA (9.7 months vs 5.8 months; P = .002). Denosumab delayed the time to increased pain interference by approximately 1 month compared with ZA (denosumab, 16.0 months; ZA, 14.9 months; P = .09). The time to pain improvement (P = .72) and the time to decreased pain interference (P = .92) were similar between the groups. Fewer denosumab-treated patients reported increased analgesic use from no/low use at baseline to strong opioid use.
  
  
  CONCLUSIONS
  Denosumab demonstrated improved pain prevention and comparable pain palliation compared with ZA. In addition, fewer denosumab-treated patients shifted to strong opioid analgesic use.
authors.affiliation: University of Texas, MD Anderson Cancer Center, Department of Symptom Research, Houston, Texas 77030, USA. ccleeland@mdanderson.org
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cleeland
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Body
authors.forename: Alison
authors.initials: A
authors.lastname: Stopeck
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
authors.forename: Lesley
authors.initials: L
authors.lastname: Fallowfield
authors.forename: Susan D
authors.initials: SD
authors.lastname: Mathias
authors.forename: Donald L
authors.initials: DL
authors.lastname: Patrick
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
authors.forename: Katia
authors.initials: K
authors.lastname: Tonkin
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Richard
authors.initials: R
authors.lastname: de Boer
authors.forename: Stefania
authors.initials: S
authors.lastname: Salvagni
authors.forename: Celia Tosello
authors.initials: CT
authors.lastname: Oliveira
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
authors.forename: Qi
authors.initials: Q
authors.lastname: Jiang
authors.forename: Roger
authors.initials: R
authors.lastname: Dansey
authors.forename: Ada
authors.initials: A
authors.lastname: Braun
authors.forename: Karen
authors.initials: K
authors.lastname: Chung
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D000069448:Denosumab; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; 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