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: Charles S Cleeland, Jean-Jacques Body, Alison Stopeck, Roger von Moos, Lesley Fallowfield, Susan D Mathias, Donald L Patrick, Mark Clemons, Katia Tonkin, Norikazu Masuda, Allan Lipton, Richard de Boer, Stefania Salvagni, Celia Tosello Oliveira, Yi Qian, Qi Jiang, Roger Dansey, Ada Braun, Karen Chung
• Journal: Cancer (Cancer) Vol. 119 Issue 4 Pg. 832-8 (Feb 15 2013) ISSN: 1097-0142 [Electronic] United States
• PMID: 22951813 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Cancer Society.

Chemical References

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

Topics

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