Denosumab Reduces Tumor Giant Cells in Giant-Cell Tumor of the Bone

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(ChemotherapyAdvisor) – Denosumab significantly reduced or eliminated RANK-positive tumor giant cells in patients with giant-cell tumor of bone (GCTB), results of a phase 2 study in Clinical Cancer Research reported.

“Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone,” Sant P. Chawla, MD, of the Santa Monica Oncology Center, Santa Monica, CA, and colleagues reported.

Currently, radical surgery is the only treatment option for this rare tumor, which primarily affects younger people. “In our study, the use of denosumab allowed patients to avoid radical surgery and prevented recurrence. We hope that in the future, its use may make it possible to avoid surgery completely,” said Dr. Chawla.

In the study, 20 adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120mg every 4 weeks; additional doses were given on days 8 and 15.

At baseline, tumor samples “were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone,” they reported.

Following treatment, a decrease of ≥90% in tumor giant cells and a reduction in tumor stromal cells were observed in all samples. “In these analyses, 13 patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells,” they reported.

A multinational study is currently enrolling patients with GCTB to confirm these results, and denosumab may also be evaluated as neoadjuvant therapy prior to surgery.

The study was funded by Amgen.


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