Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial

Ann Oncol. 2015 Oct;26(10):2149-54. doi: 10.1093/annonc/mdv307. Epub 2015 Jul 23.

Abstract

Background: Giant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB.

Patients and methods: Seventeen patients with GCTB were enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor response was evaluated prospectively by an independent imaging facility on the basis of prespecified criteria.

Results: The proportion of patients with an objective tumor response was 88% based on best response using any tumor response criteria. The proportion of patients with an objective tumor response using individual response criteria was 35% based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based on inverse Choi criteria. The median time of study treatment was 13.1 months.

Conclusion: The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB.

Keywords: RANKL; denosumab; giant cell tumor of bone; objective tumor response; primary bone tumor.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Denosumab / therapeutic use*
  • Female
  • Follow-Up Studies
  • Giant Cell Tumor of Bone / drug therapy*
  • Giant Cell Tumor of Bone / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Young Adult

Substances

  • Bone Density Conservation Agents
  • Denosumab