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U.S. Department of Health and Human Services

Drugs

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Denosumab

On June 13, 2013, the U. S. Food and Drug Administration approved denosumab (Xgeva injection, for subcutaneous use, Amgen Inc.) for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. 

Denosumab’s approval was based on demonstration of durable objective responses observed in two multicenter open label trials enrolling adult and skeletally mature adolescents with histologically confirmed, measurable giant cell tumor of bone.  These tumors were either recurrent, unresectable, or were located where planned surgery was likely to result in severe morbidity. Patients received 120 mg denosumab subcutaneously every 4 weeks with additional doses on days 8 and 15 of the first month.
 
A total of 304 patients received denosumab.  The median age was 33 years (range: 13-83 years) and a total of 10 patients were skeletally mature adolescents (13-17 years). Radiographic assessments at baseline and following denosumab treatment were available for 187 (61%) patients. A retrospective determination of objective response was performed by an independent review committee using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1). 
 
An objective response was identified in 47 of 187 patients for an overall response rate of 25% (95% CI: 19, 32). All responses were partial responses. The estimated median time to response was 3 months. In the 47 patients with an objective response, the median duration of follow-up was 20 months (range: 2- 44 months), and 51% (24/47) had responses lasting at least eight months. Three patients experienced disease progression following an objective response. 
 
Safety data was evaluated in 304 patients with giant cell tumor of bone who received at least one dose of denosumab. Of these patients, 145 were treated for at least one year. The most common adverse reactions were arthralgia, headache, nausea, back pain, fatigue, and pain in the extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis. 
 
The recommended dose and schedule of denosumab for the treatment of giant cell tumor of bone is 120 mg administered subcutaneously every four weeks with additional 120 mg doses on days 8 and 15 of the first month.
 
Full prescribing information is available at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125320s094lbl.pdf
 
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).