Xgeva by Amgen, Inc

Xgeva has received FDA approval for a new indication, the treatment of adults and skeletally mature adolescents with giant cell tumor of bone.

Amgen’s Xgeva (denosumab) has received FDA approval for its new indication for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone (GCTB) that is unresectable or for whom surgical resection is likely to result in severe morbidity. Xgeva had previously been approved and available for prevention of skeletal-related events in patients with bone metastases from solid tumors. The approval carries the limitation that Xgeva is not approved for prevention of skeletal-related events in patients with multiple myeloma.¹

GCTB usually occurs in people 20 to 40 years of age and is characterized by a bone-destructive tumor that often leads to fractures, joint dysfunction, deformity, or amputation. Most tumors occur in the long bones of the body, with rare cases spreading to the lungs. About 300 to 800 new cases of GCTB are diagnosed each year in the United States, with about 18% to 20% of cases being unresectable.²

PHARMACOLOGY AND PHARMACOKINETICS

Xgeva is a RANK ligand (RANKL) inhibitor. RANKL is required for the formation, function, and survival of osteoclasts. Xgeva binds to RANKL to prevent it from activating its receptor, RANK, on the surface of osteoclasts, their precursors, and osteoclast-like giant cells.^1,2

After subcutaneous administration, the bioavailability of Xgeva is 62%. Its mean elimination half-life is 28 days. The pharmacokinetics of Xgeva are not affected by age, gender, or race. The pharmacokinetics have not been studied in pediatric patients or in patients with hepatic impairment. Renal impairment did not affect the pharmacokinetics of Xgeva.¹

DOSAGE AND ADMINISTRATION

When used to treat GCTB, Xgeva should be given as a subcutaneous injection of 120 mg every 4 weeks, with additional 120-mg doses on days 8 and 15 during the first month of treatment. The injection should be given in the upper arm, upper thigh, or abdomen. Patients should also receive calcium and vitamin D as needed to treat or prevent hypocalcemia.¹

CLINICAL TRIALS

The safety and efficacy of Xgeva in the treatment of GCTB was evaluated in 2 open-label trials in patients with GCTB that was either recurrent or unresectable or for which planned surgery was likely to result in severe morbidity. The primary efficacy outcome measure was objective response rate using modified Response Evaluation Criteria in Solid Tumors. Of the total of 187 patients, the overall objective response rate was 25%. All responses were partial responses. The estimated median time to response was 3 months. Fifty-one percent of responders (24 patients) had a duration of response lasting at least 8 months, and 3 patients experienced disease progression after an objective response.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Xgeva is contraindicated in patients with hypocalcemia or known clinically significant hypersensitivity to Xgeva. Patients should not use Prolia (Amgen) during treatment with Xgeva, as the 2 products contain the same active ingredient. Patients should be monitored for hypersensitivity reactions, including anaphylaxis, and treatment should be discontinued if a clinically significant reaction occurs.

Severe symptomatic hypocalcemia, including fatalities, has been reported during treatment with Xgeva. Hypocalcemia should be corrected prior to starting treatment with Xgeva. Calcium levels should be monitored during treatment, and patients should be supplemented with calcium and vitamin D as appropriate. Monitor for osteonecrosis of the jaw before and during treatment with Xgeva. Invasive dental procedures should be avoided. Patients with thigh or groin pain should be evaluated to rule out femoral fracture.

Xgeva is Pregnancy Category D. Women of childbearing potential should use highly effective contraception during treatment and for 5 months after Xgeva is discontinued. Xgeva should not be used during breast-feeding. Xgeva should not be used in pediatric patients.

Patients with a creatinine clearance of less than 30 mL/min or who are receiving dialysis are at risk for hypocalcemia and should receive calcium and vitamin D supplementation. The most common adverse reactions (≥10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity.¹ SPT

References

• Xgeva [package insert]. Thousand Oaks, CA: Amgen; 2013. http://pi.amgen.com/united_states/xgeva/xgeva_pi.pdf. Accessed November 2013.
• FDA approves Amgen’s Xgeva (denosumab) for the treatment of giant cell tumor of bone: Xgeva becomes first FDA-approved treatment for this rare disease [press release]. wwwext.amgen.com/media/media_pr_detail.jsp?releaseID=1829715. Accessed November 2013.

About the Author

Monica Holmberg, PharmD, BCPS, earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.