Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?

Eur J Cancer. 2017 May;76:118-124. doi: 10.1016/j.ejca.2017.01.028. Epub 2017 Mar 17.

Abstract

Background: Giant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly 'GCTB-schedule' (120 mg per 12/year, 1440 mg total dose/year) are lacking.

Methods: Patients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated.

Results: Ninety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6-45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13-76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9-115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7-15 months).

Adverse events: Overall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84-100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%).

Conclusions: Prolonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB.

Keywords: Denosumab; GCTB; Giant-cell tumour of the bone; ONJ; Receptor activator of nuclear factor κB ligand.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / epidemiology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Cohort Studies
  • Denosumab / administration & dosage*
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Femoral Neoplasms / drug therapy
  • Femoral Neoplasms / pathology
  • Giant Cell Tumor of Bone / diagnostic imaging
  • Giant Cell Tumor of Bone / drug therapy*
  • Giant Cell Tumor of Bone / secondary
  • Humans
  • Ischium
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Radius / diagnostic imaging
  • Retrospective Studies
  • Sacrum
  • Skull Neoplasms / drug therapy
  • Skull Neoplasms / pathology
  • Spinal Neoplasms / drug therapy
  • Spinal Neoplasms / pathology
  • Tibia
  • Time Factors
  • Young Adult

Substances

  • Bone Density Conservation Agents
  • Denosumab