Experimental agent denosumab active against giant cell tumor of bone

In a small phase II study, 87% of patients with recurrent or unresectable giant cell tumor of bone had a significant tumor response to the humanized monoclonal antibody denosumab – a finding that warrants further exploration of the experimental agent as long-term therapy for this rare cancer, according to an investigator at the annual meeting of the American Society of Clinical Oncology.
A total of 9 of 15 patients in an interim analysis had a histologic response indicating either decimation or elimination of the tumor by denosumab, and 4 had a radiographic response indicating stable disease with no evidence of additional progression, said Dr. David Thomas, group leader of the Sarcoma Genomics and Genetics Laboratory at Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia.
Denosumab targets the RANK ligand (RANKL), a mediator of osteoclast formation, function, and survival.
”Histologic results showed almost complete or complete elimination of the giant cells,” Dr. Thomas said in a clinical science symposium. “In some cases, elimination of the giant cells was associated with reductions in RANKL, especially in the tumor, raising the question of whether with prolonged treatment with this agent we might be able to eliminate the cells that drive giant cell tumor of bone.”
The investigators also observed that some patients in the study, funded by Amgen Inc., the maker of denosumab, had evidence of reduction in tumor activity on positron emission tomography scans, stabilization of tumors in bone, a decrease in soft tissue expansion outside the bone, and, in three patients, evidence of new bone formation and repair.
Nine patients also had a clinical benefit, reflected as reductions in pain and increased range of motion sufficient to allow some of them to return to work.
A total of 35 adults with either resectable or unresectable giant cell tumors were enrolled in the 1-year, open label phase II study. They received 120 mg of denosumab once monthly, with loading doses on the 8th and 15th days of the first treatment month.
The primary study end point was tumor response, defined as an elimination of at least 90% of giant cells, or no radiographic evidence of progression of the target lesion at week 25.
In all, 15 patients were evaluable for efficacy, based on the availability of pre- and posttreatment radiology or histology assessments. The authors found that 13 of the 15 (87%) had a tumor response: 9 of 9 with a histologic response, and 4 of 6 with a radiographic response.
Adverse events occurred in 19 of the 24 patients who have received denosumab thus far in the study. The most frequent events were headache and nasopharyngitis, each occurring in three patients. Two patients had serious adverse events – one case of depression and one of nausea and pain – but these were deemed to be unrelated to the treatment. There were also three unspecified grade 3 and higher adverse events, also determined to be unrelated to the treatment.