Denosumab is a targeted therapy to prevent bone loss. It stops progressive bone destruction and tumour spread in some patients with inoperable giant-cell tumour (GCT) of bone. An article published Online First in The Lancet Oncology reports this could change standard treatment practice. Breaking new ground, this work is the first to clearly show a promising systemic treatment option for this rare type of bone tumour.
GCT can be limb and life threatening. It causes pain, impaired function and mobility. This condition is usually benign, and surgery is the standard treatment. However, GCT can become malignant after radiation therapy or several recurrences. In some cases, patients are unable to undergo surgery because of multiple lesions, location of the tumour (for example, the spine), or because of tumour spread. These patients have limited treatment options.
Denosumab is a monoclonal antibody. It targets and disables RANK ligand which is a key mediator of osteoclast activity. It blocks the action of osteoclasts, the cells that break down bone. Denosumab has been favourable in the treatment of conditions linked to bone destruction including multiple myeloma and bone metastases. In addition, it might improve outcomes in patients with GCT.
A phase 2 trial was carried out by David Thomas from Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues. They investigated the safety and effectiveness of denosumab in patients with recurrent or inoperable GCT.
A total of 37 patients with non-malignant GCT were recruited from the USA, Australia, and Europe. They were given monthly injections of denosumab, with additional loading doses on days 8 and 15 of the first month. In addition, patients took daily calcium and vitamin D supplements.
Results indicated that 30 of 35 (86 percent) patients had a tumour response, including some who had lung lesions. There was elimination of at least 90 percent of giant cells or no radiological progression of the target lesion up to week 25.
Also, among the 31 patients who were assessed for clinical response, 26 (84 percent) reported clinical benefit. This included reduced pain and improvements in function and mobility. A total of 9 (26 percent) had bone repair. Denosumab also contributed to fast and continued suppression of bone turnover.
In total, 33 of 37 patients experienced an adverse event. The most common being pain in an extremity such as back pain and headaches. Five patients had grade 3 to 5 adverse events, only one of which was related to treatment.
The researchers explain: “These findings suggest that continued denosumab may have a therapeutic role in cases of unsalvageable GCT, particularly with pulmonary metastases, but also in the neoadjuvant setting where the drug might improve surgical outcomes.”
In an associated note, Maurice Balke from the University of Witten-Herdecke, Hospital Cologne-Merheim, Germany, and Jendrik Hardes from University Hospital Muenster, Germany greet the study. They say that it: “Might change clinical practice in the treatment of complicated GCT of bone.”
They comment that there is a need for further studies on the mechanism of action of denosumab. They suggest giving neoadjuvant treatment with denosumab to reduce tumour size before surgery for typical benign lesions.
“Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study”
David Thomas, Robert Henshaw, Keith Skubitz, Sant Chawla, Arthur Staddon, Jean-Yves Blay, Martine Roudier, Judy Smith, Zhishen Ye,Winnie Sohn, Roger Dansey, Susie Jun
DOI: 10.1016/S1470-2045(10)70010-3
Written by Stephanie Brunner (B.A.)