Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study

J Thorac Oncol. 2012 Dec;7(12):1823-1829. doi: 10.1097/JTO.0b013e31826aec2b.

Abstract

Introduction: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma.

Methods: Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC.

Results: Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA.

Conclusion: In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / mortality*
  • Bone Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Denosumab
  • Diphosphonates / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Imidazoles / therapeutic use*
  • International Agencies
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RANK Ligand / antagonists & inhibitors
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Survival Rate
  • Young Adult
  • Zoledronic Acid

Substances

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