Denosumab Reduces Burden of Giant-cell Tumor of the Bone
- Denosumab decreased tumor presence in the entire cohort.
- Some patients experienced bone regrowth.
- Drug could be first medical alternative to radical surgery.
PHILADELPHIA — Treatment with denosumab, a drug targeted against a protein that helps promote bone destruction, decreased the number of tumor giant cells in patients with giant-cell tumor of the bone, and increased new bone formation, according to the results of a phase II study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
“Giant-cell tumor of the bone is a rare tumor that affects mostly young people,” said Sant P. Chawla, M.D., director of the Santa Monica Oncology Center, Santa Monica, Calif. “Radical surgery is currently the only treatment option. 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.”
Giant-cell tumor of the bone is a benign tumor characterized by giant cells that are positive for the protein RANK ligand, which helps promote bone destruction. Currently, the only treatment option for patients with giant-cell tumor of the bone is surgery. However, patients who undergo surgery often have recurrent disease or significant morbidity, such as amputation. In addition, 25 to 30 percent of patients with this tumor have to undergo joint replacements.
Chawla and colleagues conducted this phase II study to explore the mechanism of action of denosumab, an inhibitor of RANK ligand, in the treatment of giant-cell tumor of the bone.
Twenty adult patients with recurrent or unresectable giant-cell tumor of the bone were treated with subcutaneous denosumab every four weeks. After treatment, all 20 of the patients had a decrease in giant cells of 90 percent or greater, an indicator of a reduction of tumor burden. In addition, results indicated that 65 percent of the patients had new bone growth in areas where the RANK ligand had previously caused bone destruction.
“A majority of patients with giant-cell tumor of the bone are young and have to get joint replacements, which last 15 to 20 years before a repeat surgery is needed,” Chawla said. “Now, we hopefully can do minimal surgery, avoiding a joint replacement and recurrence.”
One of the next steps in evaluating denosumab for giant-cell tumor of the bone is a much larger, multinational study that is currently enrolling patients. In addition, Chawla hopes to evaluate the use of denosumab as a presurgery, or neoadjuvant, treatment as well.
“In the future we hope to investigate giving the drug prior to surgery to see the effect it has, then remove the tumor and evaluate the pathological response,” Chawla said.
This study was funded by Amgen.
About the AACR
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
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