Bone-targeted therapy use in patients with bone metastases from lung cancer: A systematic review of randomized controlled trials

Cancer Treat Rev. 2016 Nov:50:183-193. doi: 10.1016/j.ctrv.2016.09.013. Epub 2016 Sep 20.

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.

Conclusion: 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.

Keywords: Bisphosphonates; Bone metastases; Bone targeted therapy; Denosumab; Lung cancer.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Denosumab / therapeutic use*
  • Diphosphonates / therapeutic use*
  • Disease-Free Survival
  • Fractures, Spontaneous / prevention & control*
  • Humans
  • Lung Neoplasms / pathology*
  • Randomized Controlled Trials as Topic
  • Spinal Cord Compression / etiology
  • Spinal Cord Compression / prevention & control
  • Spinal Neoplasms / complications
  • Spinal Neoplasms / drug therapy
  • Spinal Neoplasms / secondary

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Denosumab