Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid

Cancer. 2013 Feb 15;119(4):832-8. doi: 10.1002/cncr.27789. Epub 2012 Sep 5.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bone Density Conservation Agents / adverse effects*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / pathology*
  • Denosumab
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use*
  • Middle Aged
  • Pain / chemically induced
  • Pain / prevention & control*
  • Zoledronic Acid

Substances

  • Analgesics
  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Denosumab
  • Zoledronic Acid