title: Bone-targeted therapy use in patients with bone metastases from lung cancer: A systematic review of randomized controlled trials.
abstract: BACKGROUND
  Patients with advanced lung cancer commonly have bone metastases. Compared with other malignancies, the use of bone-targeted agents (e.g. bisphosphonates and denosumab) is less common in lung cancer patients. This may be due to the perception that bone-targeted agents are less effective in this population.
  
  
  OBJECTIVE
  To perform a systematic review to evaluate data from randomized trials of bone-targeted agents in lung cancer patients with bone metastases.
  
  
  METHODS
  A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials through May 2015 was performed. Randomized trials of bone-targeted therapies in lung cancer patients with bone metastases were sought. Outcomes studied included skeletal related events (SREs), pain, quality of life, progression-free survival and overall survival. Random effects meta-analyses were planned if studies were judged homogeneous.
  
  
  RESULTS
  Of 632 abstracts, 17 publications describing 13 studies were included. Sample sizes ranged between 50 and 1776. Of 3379 patients, 1903 had lung cancer, with subgroup data available for 8 of 13 studies. Patient demographics were comparable, but enrollment criteria and endpoints were heterogeneous across studies, precluding meta-analysis. Study-specific results suggested that bone-modifying agents reduce the incidence of SREs and bone pain in lung cancer patients. Three studies suggested a survival benefit.
  
  
  CONCLUSIONS
  Data from included trials suggests benefit of bone-targeted agents in lung cancer for the prevention of SREs and bone pain. There is a trend toward improvement in overall survival and progression-free survival, although further research is needed. Impact on quality of life and key subgroups for benefit both require future research.
authors.affiliation: Division of Medical Oncology and Department of Medicine, University of Ottawa, Ottawa, Canada. Electronic address: nlevasseur@toh.on.ca.
authors.forename: Nathalie
authors.initials: N
authors.lastname: LeVasseur
authors.affiliation: Division of Medical Oncology and Department of Medicine, University of Ottawa, Ottawa, Canada; Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Ottawa General Hospital, Ottawa, Canada.
authors.forename: Risa
authors.initials: R
authors.lastname: Shorr
authors.affiliation: Division of Medical Oncology and Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Carmel
authors.initials: C
authors.lastname: Jacobs
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D000069448:Denosumab / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005598:Fractures, Spontaneous / Q000517:prevention & control*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D013117:Spinal Cord Compression / Q000209:etiology / Q000517:prevention & control; D013125:Spinal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab
keywords: Bisphosphonates; Bone metastases; Bone targeted therapy; Denosumab; Lung cancer