The anti-RANKL antibody denosumab is safe and effective in patients with giant cell tumor of bone.

  • Major finding: The anti-RANKL antibody denosumab is safe and effective in patients with giant cell tumor of bone.

  • Concept: Neoplastic stromal cells express high levels of RANKL, and osteoclast-like giant cells express RANK.

  • Impact: Denosumab treatment leads to objective responses and reduces the need for morbid surgery.

Giant cell tumor of bone (GCTB) is a generally benign but locally aggressive tumor with no standard treatment other than surgery. Surgery can be curative, but can cause significant morbidity and is not always possible. Local recurrence or metastasis also occurs in a small percentage of patients with GCTB. GCTB is composed of neoplastic stromal cells of an osteoblastic origin that express high levels of receptor activator of NF-κB ligand (RANKL), which activates RANK-expressing osteoclast-like giant cells that mediate the destruction of surrounding bone. Chawla and colleagues therefore evaluated the activity of the anti-RANKL monoclonal antibody denosumab in an open-label phase II trial in patients with surgically unsalvageable GCTB and patients planning to undergo surgeries that would cause significant morbidity. The primary endpoint was safety, and secondary endpoints included time to disease progression in the unsalvageable GCTB cohort and no requirement for surgery after 6 months of treatment in the resectable GCTB cohort. Denosumab was generally well tolerated, and serious adverse events were rare. Of 169 patients with surgically unsalvageable GCTB, 163 (96%) did not experience disease progression after a median follow-up time of 13 months. Of 71 patients with resectable GCTB who were planning to have surgery, 64 (90%) did not have surgery after 6 months of denosumab treatment. Over half of those who did eventually undergo surgery by the time of the analysis had a less drastic surgical procedure than originally planned. Sustained disease control (including complete responses, partial responses, or disease stabilization) was observed in 109 of 111 (98%) evaluable patients by a retrospective imaging analysis. Based on the results of this trial, denosumab was recently approved by the FDA for the treatment of unresectable GCTB in adults and skeletally mature adolescents.

Chawla S, Henshaw R, Seeger L, Choy E, Blay JY, Ferrari S, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 2013;14:901–8.

Note:Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.