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.

For policy decision makers: A prior bone complication can markedly increase the risk for developing a subsequent bone complication For policy decision makers: A prior bone complication can markedly increase the risk for developing a subsequent bone complication

*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.2

Your formulary decisions matter for patients like:

Helen, 63, living with breast cancer and bone metastases. She is currently being treated with zoledronic acid (ZA) due to step therapy and experienced a bone complication

Consider the total cost of care and the downstream consequences of using ZA step therapy policies that restrict using XGEVA® first for patients like Helen3

For more information, click on the category headings below

Drug acquisition
Drug administration

Hospitalization
Outpatient
Emergency department visits
Long-term care and hospice
Physical therapy and devices
Skilled nursing facility
Strong opioids
Adverse events

Caregiver burden
Transportation

Short-term disability and
productivity loss

SRE-related
Route of
administration related
Adverse events related

For policy decision makers: Consider the total cost of care and downstream health economic consequences of using step therapy to restrict XGEVA® access. For policy decision makers: Consider the total cost of care and downstream health economic consequences of using step therapy to restrict XGEVA® access.

Sensitivity analyses3

Based upon a sensitivity analysis, the incremental value is most sensitive to changes in the efficacy of XGEVA® vs ZA in preventing first SRE and adjustment for real-world SRE occurrence

Model assumptions and limitations3

Step through ZA to XGEVA® in the model is based only on the occurrence of a first SRE following treatment initiation

To stay consistent with prior analyses evaluating the cost-effectiveness of XGEVA®, the SRE rates for XGEVA® were calculated using SRE rates for ZA from the three solid tumor phase 3 pivotal trials and applying efficacy. When XGEVA® rates from the trials were modeled in a scenario analysis, the incremental value delivered by XGEVA® improved by 3%, while the difference in total direct costs remained approximately 5%

SRE costs in patients with other solid tumors were assumed to be the average of the costs in breast and prostate cancer

The results should be interpreted within the context of the data inputs and modeling assumptions used as the results may be sensitive to changes in these inputs

Costs of health services were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters

The mortality rate was extrapolated to reflect a time horizon of 3 years, which may or may not accurately reflect actual outcomes

Results from observational matched cohort research using MarketScan® commercial and Medicare supplemental databases among 47,052 patients with bone metastases secondary to solid tumors, including breast, prostate, and lung cancer, who did not receive a bone-targeting agent between 2008 and 3/31/2015. 13% of patients had at least one SRE prior to bone metastases diagnosis.1

Important Safety Information

Hypocalcemia

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. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. 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.

Hypersensitivity

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.

Drug Products with Same Active Ingredient

Patients receiving XGEVA® should not take Prolia® (denosumab).

Osteonecrosis of the Jaw

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 Subtrochanteric and Diaphyseal Femoral Fracture

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.

Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone (GCTB) and in Patients with Growing Skeletons

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) Following Treatment Discontinuation

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.

Embryo-Fetal Toxicity

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®.

Adverse Reactions

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.

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.

Please see Full Prescribing Information.

References

  1. Data on file, Amgen; 2018.
  2. XGEVA® (denosumab) prescribing information, Amgen.
  3. Data on file, Amgen; [XGEVA® First vs ZA Step-Edit Economic Model; 2018].