Denosumab (Xgeva)

General information

Class/mechanism: Human IgG2 monoclonal antibody that inhibits RANK ligand (RANKL). RANKL promotes the formation, function, and survival of osteoclasts, which are responsible for bone resorption.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Disease-specific information

For now this will be a gathering point for RCTs examining the use of this agent, which does not have clear antineoplastic properties with the exception of giant cell tumor of bone; in the future this information may be moved to separate page(s).

Prostate cancer

• Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011 Mar 5;377(9768):813-22. Epub 2011 Feb 25. link to original article link to PMC article PubMed
• Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damião R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gómez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012 Jan 7;379(9810):39-46. Epub 2011 Nov 15. link to original article link to PMC article PubMed

Diseases for which it is used

• Giant-cell tumor of bone

Patient drug information

• Denosumab (Xgeva) patient drug information (Chemocare)
• Brief patient counseling information can be found on page 15 of the Denosumab (Xgeva) package insert
• Denosumab (Xgeva) patient drug information (UpToDate)

History of changes in FDA indication

• 2010-06-01: Approved (as Prolia) for treatment of postmenopausal women with osteoporosis at high risk for fracture.
• 2010-11-18: Approved for prevention of skeletal-related events in patients with bone metastases from solid tumors.
• 2013-06-13: Approved for 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. (Based on Amgen 20040215 & Amgen 20062004)

History of changes in EMA indication

• 2010-05-26: Initial authorization as Prolia
• 2011-07-13: Initial authorization as Xgeva

History of changes in Health Canada indication

• 2011-05-10: Initial notice of compliance

History of changes in PMDA indication

• 2012-01-18: Initial approval for the treatment of bone lesions due to multiple myeloma and bone lesions due to bone metastasis of solid tumor.
• 2014-05-23: New additional indication and a new dosage for the treatment of giant cell tumor of bone.

Also known as

• Brand names: Prolia, Ranmark, Xgeva