XGEVA

Last Updated: December 23, 2010

 

Manufacturer: Amgen, Inc. Pharmacological Class: Osteoclast inhibitor (RANKL inhibitor) Active Ingredient(s): Denosumab 120mg/vial (70mg/mL); soln for SC inj; preservative-free.

Indication(s):

Prevention of skeletal-related events (SRE) in patients with bone metastases from solid tumors. Not for preventing SRE with multiple myeloma.

Pharmacology:

In patients with solid tumors with osseous metastases, an increase in osteoclast activity is a mediator of bone pathology. This increased osteoclast activity is stimulated by a substance called receptor activator of nuclear factor kappa-B ligand, or RANKL. Denosumab is a monoclonal antibody that binds to human RANKL. It prevents RANKL from interacting with its receptors on the surfaces of osteoclasts and their precursors, thereby inhibiting osteoclast formation, function, and survival.

Clinical Trials:

The safety and efficacy of Xgeva in the prevention of skeletal-related events (eg, pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression) in patients with bone metastases from solid tumors were evaluated in three randomized, double-blind, active-controlled trials that compared this drug to zoledronic acid. In each trial, the main outcome measure was to show noninferiority of time-to-first skeletal-related event (SRE) with denosumab as compared to zoledronic acid. If primary endpoint (noninferiority) was reached, secondary endpoints for Time to First SRE and Time to First and Subsequent SRE were tested for superiority.

Trial 1 enrolled patients with advanced breast cancer and bone metastasis. Trial 2 enrolled adults with bone metastasis from solid tumors, other than prostate or breast cancer, or with multiple myeloma. Trial 3 enrolled patients with castrate-resistant prostate cancer and bone metastasis.

Xgeva delayed the time to first SRE following randomization as compared to zoledronic acid in patients with breast or castrate-resistant prostate cancer with osseous metastases. In patients with bone metastasis due to other solid tumors or lytic lesions due to multiple myeloma, Xgeva was noninferior to zoledronic acid in delaying time to first SRE after randomization.

Overall survival and progression-free survival were similar between arms in all three trials, but mortality was higher with Xgeva in a subgroup of patients with multiple myeloma; therefore, it should not be used in these patients.

Legal Classification:

Rx

Adults:

Give by SC inj into upper arm, upper thigh, or abdomen. 120mg once every 4 weeks.

Children:

Not recommended (interferes with bone growth and dentition).

Warnings/Precautions:

Correct hypocalcemia before starting; ensure adequate daily calcium, magnesium, and Vit.D intake, esp. in renal impairment (CrCl<30mL/min). Monitor calcium, phosphorus, magnesium levels in susceptible patients (eg, severe renal impairment, receiving dialysis). Monitor for osteonecrosis of the jaw. Do baseline oral exam and preventive dentistry before and regularly during therapy. Maintain good oral hygiene. Avoid invasive dental procedures during treatment. Pregnancy (Cat.C). Nursing mothers: avoid (may impair mammary gland development/lactation).

Interaction(s):

Concomitant drugs that can lower calcium levels; monitor.

Adverse Reaction(s):

Fatigue, asthenia, hypophosphatemia, GI upset, dyspnea, osteonecrosis of jaw, severe hypocalcemia.

Notes:

Encourage women who become pregnant during Xgeva treatment to enroll in Amgen’s Pregnancy Surveillance program. To enroll call (800) 77-AMGEN.

How Supplied:

Single-use vial (1.7mL)—1

Last Updated:

8/12/2011