Indication
XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
From three clinical trials comparing XGEVA® with ZA in patients with bone metastases from solid tumors
Most common ARs reported with XGEVA® in ≥25% of patients1
aLaboratory-derived and below the central laboratory lower limit of normal [8.3–8.5 mg/dL (2.075–2.125 mmol/L) for calcium and 2.2–2.8 mg/dL (0.71–0.9 mmol/L) for phosphorus].1
AR, adverse reaction; ZA, zoledronic acid.
† Acute phase reaction events are defined as those occurring within the first 3 days of treatment.
Q4W, every 4 weeks; ZA, zoledronic acid.
From a clinical trial comparing XGEVA® with ZA in patients with multiple myeloma
Common ARs reported with XGEVA® in ≥10% of patients1,4
In an ad hoc analysis,
Acute phase reactions were reported in fewer patients with XGEVA® than with ZA5,6,†,‡
XGEVA® 120 mg Q4W: n=46 (5%); ZA 4 mg Q4W: n=74 (9%)
†Acute phase reaction events were defined as those occurring within the first 3 days of treatment, the most common being pyrexia, fatigue, bone pain, arthralgia, and chills.6
‡Not powered for statistical significance.
Q4W, every 4 weeks.
Rates of treatment-emergent adverse events were similar in patients treated with XGEVA® and ZA5
With XGEVA®, fewer patients suffered from renal AEs vs ZA patients5
§N is the number of patients with baseline serum creatinine >2 mg/dL.5
**N is the number of patients with non-missing baseline values of serum creatinine.5
AEs, adverse events.
Video Length [9:44]
Open-Label Extension 
Open-Label Extension 
*A safety and efficacy evaluation of the primary treatment phase occurred during a double-blinded extension for the 3 independent trials to determine appropriate evaluable patients for an open-label extension phase. Researchers in breast and prostate cancer trials were eligible to continue their patients into a 2-year, open-label extension phase, and the patients in those trials could continue on or transition to XGEVA® 120 mg Q4W at their next scheduled dose.8
IV, intravenous; MM, multiple myeloma; OST, other solid tumors; Q4W, every 4 weeks; SC, subcutaneous.
Osteonecrosis of the Jaw 
Osteonecrosis of the Jaw 
SCROLL DOWN FOR RATES IN SOLID TUMORS AND MULTIPLE MYELOMA
Majority of patients with ONJ had known risk factors:
In clinical trials in patients with cancer, the incidence of ONJ was higher with longer duration of exposure. 1
Advise patients to avoid invasive dental procedures while taking XGEVA® 1
In a clinical trial evaluating XGEVA® in patients with non-metastatic prostate cancer (a patient population for which XGEVA® is not indicated), with longer treatment exposure of up to 7 years, the patient-year adjusted incidence of ONJ was 1.1% during the first year of treatment, 3.0% in the second year, and 7.1% per year thereafter. 1
SRE, skeletal-related event.
Majority of patients who developed ONJ had known risk factors:
Advise patients to avoid invasive dental procedures while taking XGEVA® 1
*Represents initial ONJ grade of triggering event. There were no Grade 4 or Grade 5 ONJ events.4
SCROLL DOWN FOR MANAGEMENT STRATEGIES IN SOLID TUMORS AND MULTIPLE MYELOMA
Management strategies used in patients who experienced ONJ in the XGEVA® clinical trials
Oral rinses and antibiotics were frequently used to treat ONJ in the trials 5,8
HYPOCALCEMIA 
HYPOCALCEMIA 
Across 3 head-to-head phase 3 studies of more than 5,600 patients,
Advise patients
Studies in patients with renal impairment
In clinical trials of 87 patients with varying degrees of renal dysfunction, including patients on dialysis, the degree of renal impairment has no effect on the pharmacokinetics and pharmacodynamics of XGEVA®1
In one study, patients (n=55) with varying degrees of renal function* received a single 60 mg SC dose of denosumab
In a second study, patients (n=32) with severe renal dysfunction† were given two 120 mg SC doses of denosumab
In both studies, greater risk of developing hypocalcemia was observed with increasing renal impairment and with inadequate/no calcium supplementation. In the second study, 96% of patients experienced mild to moderate hypocalcemia.1
In patients with renal impairment, monitor calcium levels and calcium and vitamin D intake.1
*Renal function ranging from normal through end-stage renal disease requiring dialysis.1
†Creatinine clearance <30mL/min and/or on dialysis.1
SC, subcutaneous.
Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be closely monitored. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.
XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.
Patients receiving XGEVA® should not take Prolia® (denosumab).
Osteonecrosis of the jaw (ONJ) has been reported in patients receiving XGEVA®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with cancer, the incidence of ONJ was higher with longer duration of exposure.
Patients with a history of tooth extraction, poor oral hygiene, or use of a dental appliance are at a greater risk to develop ONJ. Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections.
Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®. Consider temporarily interrupting XGEVA® therapy if an invasive dental procedure must be performed.
Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Atypical femoral fracture has been reported with XGEVA®. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Clinically significant hypercalcemia requiring hospitalization and complicated by acute renal injury has been reported in XGEVA®-treated patients with GCTB and in patients with growing skeletons within one year of treatment discontinuation. Monitor patients for signs and symptoms of hypercalcemia after treatment discontinuation and treat appropriately.
Multiple vertebral fractures (MVF) have been reported following discontinuation of treatment with denosumab. Patients at higher risk for MVF include those with risk factors for or a history of osteoporosis or prior fractures. When XGEVA® treatment is discontinued, evaluate the individual patient’s risk for vertebral fractures.
XGEVA® can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA® is expected to result in adverse reproductive effects.
Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.
The most common adverse reactions in patients receiving XGEVA® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.
For multiple myeloma patients receiving XGEVA®, the most common adverse reactions were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. The most common serious adverse reaction was pneumonia. The most common adverse reaction resulting in discontinuation of XGEVA® was osteonecrosis of the jaw.
XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
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Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be..
