Denosumab in GCT (phase 2)

Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study.

Thomas D, Henshaw R, Skubitz K, et al. The Lancet. Oncology 2010 · PMID 20149736 · doi:10.1016/s1470-2045(10)70010-3

Question

Does RANKL inhibition with denosumab produce responses in recurrent or unresectable giant cell tumour of bone?

Design

Open-label, single-arm, multicentre phase 2 study.

Patients

Adults with recurrent or unresectable giant cell tumour of bone.

Intervention

Subcutaneous denosumab 120 mg every 4 weeks with loading doses

Comparison

None (single arm)

Primary outcome

Tumour response (histological elimination of giant cells or radiological non-progression) at 25 weeks

Key result

86% of evaluable patients responded, including every patient assessed histologically (near-elimination of giant cells); serious adverse events were uncommon and none was judged treatment related.

Limitations

Small, uncontrolled study with short follow-up; later work showed recurrence after stopping denosumab and higher local recurrence when it was used before curettage.

Impact on practice

Established denosumab as a treatment option for unresectable or surgically morbid GCT, while curettage with adjuvants remains first-line for resectable lesions.