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.
SIGNS & SYMPTOMS OF SKELETAL-RELATED EVENTS
The threat of bone complications* may be present even if pain is not2
†Data from the placebo arm (n=208) of a retrospective analysis evaluating the efficacy of an IV bisphosphonate in the reducing of bone complications and bone pain in men with bone metastases from prostate cancer. In this trial, bone complications or SREs were defined as pathologic fracture, irradiation of or surgery to bone, spinal cord compression, and hypercalcemia.2
Don't wait to start a bone-targeting agent (BTA)
Video Length [15:01]
Watch two physicians discuss initiating a BTA for a hypothetical patient with breast cancer and bone metastases who isn't experiencing bone pain.
BONE METASTASES RISK IN SOLID TUMORS
People with bone metastases from solid tumors are at risk of suffering one or more bone complications
BREAST CANCER RISK
In the placebo arm of a randomized clinical trial
of women with breast cancer and bone metastases experienced a bone complication3,*
PROSTATE CANCER RISK
In the placebo arm of a randomized clinical trial
of men with prostate cancer and bone metastases experienced a bone complication within 2 years4,†
*Data from the placebo arm (n=384) of a randomized clinical trial evaluating the efficacy of an IV bisphosphonate in the reduction of bone complications in women with bone metastases from breast cancer. In this trial, bone complications or SREs were defined as pathologic fracture, irradiation of or surgery to bone, spinal cord compression, and hypercalcemia.3
†Data from the placebo arm (n=208) of a randomized trial evaluating the efficacy of an IV bisphosphonate in the reduction of bone complications in men with bone metastases from prostate cancer. In this trial, bone complications or SREs were defined as pathologic fracture, surgery to bone, radiation to bone, spinal cord compression, and change in antineoplastic therapy to treat bone pain.4
IV, intravenous; SRE, skeletal-related event.
Despite this risk, more than half of patients remain untreated with a BTA.5,‡
‡Estimates for the prevalence of bone-targeting agent use are based on Decision Resource Group (DRG) claims data (N=61,949) ending February 2018.5
Survival rates in metastatic cancer are at least 5 years
for many patients with breast and prostate cancer, and some with lung cancer8-10
A panel discussion with Dr. Francis Arena and Dr. Noam Drazin
Video Length [21:10]
PROSTATE CANCER AND BONE METASTASES
A panel discussion with Dr. Neal Shore and Dr. Jorge Garcia
Video Length [11:23]
BONE METASTASES RISK IN MULTIPLE MYELOMA
Multiple myeloma puts patients’ bones at risk for bone complications, which continues throughout the course of disease
In patients with multiple myeloma,
In a retrospective cohort study of 165 multiple myeloma patients
experienced pathologic fractures during the course of their disease6,*
One fracture can lead to another11
more likely to experience a subsequent fracture after a prior bone complication†
*In a retrospective cohort study of 165 multiple myeloma patients, majority of (57%) pathologic fractures caused by lytic bone lesions, mainly in the vertebrae and ribs.6
†In a retrospective analysis of 220 patients who had an SRE at baseline, 88% experienced a fracture vs 12% who did not.11
Despite NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommending treatment with a BTA for up to 2 years to prevent bone complications, including fractures, in patients receiving primary therapy for multiple myeloma…12
…LESS THAN 50% of patients are on a BTA at 12 months following diagnosis, often only receiving one after the onset of a bone complication13,†
‡Based on a 2017 retrospective analysis of electronic health records from oncology clinics across the United States (Flatiron Health, Inc.) that linked to the MarketScan® claims databases. Patients ≥18 years with a new multiple myeloma diagnosis (ICD-9, 203.00; ICD-10, C90.00), 2011-2016. Patients were excluded if they had an IV bisphosphonate within 6 months of the multiple myeloma diagnosis, concurrent cancer in the 12 months prior to diagnosis, or zero resource use in the 30 days following the diagnosis. The cumulative incidence of IV bisphosphonate initiation was estimated using competing risk models to account for death. Analysis excluded XGEVA® as it was not approved in this patient population at that time.13
Active multiple myeloma is defined as clonal bone marrow cells >10% or biopsy-proven bony or extramedullary plasmacytoma plus any one or more of the following myeloma-defining events (MDEs)
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HyperCalcemia
Serum calcium >1 mg/dL above ULN or >11 mg/dL14
of patients15
Renal insufficiency§
CrCl <40 mL/min or serum creatinine >2 mg/dL14
of patients16
Anemia
Hemoglobin >20 g/L below LLN or <100 g/L14
of patients15
Bone lesions
1 or more lesions on skeletal radiography, CT, or PET-CT14,**
of patients17,18
Bone lesions are the most prevalent CRAB feature present at diagnosis16,17
§Multiple myeloma directly harms the kidneys, potentially complicating bone-targeting treatment for patients with renal impairment.16,18
**F-fluorodeoxyglucose PET with CT.
CrCl, creatinine clearance; CT, computed tomography; LLN, lower limit of normal; PET, positron emission tomography; ULN, upper limit of normal.
FLC, free light chain; MRI, magnetic resonance imaging.
will develop lytic bone lesions, which often
lead to bone complications6,18
During the course of their disease, up to
60% develop renal impairment19
Video Length [2:45]
Watch how RANKL can lead to excessive bone resorption when overproduced by multiple myeloma cells.20
RANKL, RANK ligand.
COST IMPLICATIONS
Bone complications can be costly
Average cost of bone complications in patients with commercial insurance21,*
Average cost of bone complications in patients with Medicare21,*
*This retrospective, observational cohort study used administrative claims data from the IBM Watson Health MarketScan® Commercial and Encounters Database and the Medicare Supplemental and Coordination of Benefits Database from 2015 to 2018. SRE cohorts were comprised of patients with newly diagnosed bone metastasis secondary to a solid tumor and with any bone metastasis from 2016 to 2018. Patients were classified into case and control groups based on the presence and number of SREs. Patients with multiple myeloma during this period were excluded.21
†In the primary approach, costs of SREs were estimated based on differences in healthcare costs between matched patients with only 1 SRE vs no SRE (similar to the approach taken by others), and with ≥2 SREs vs 1 SRE. All-cause healthcare costs for both cases and controls were captured, and the difference was considered as costs attributable to the SRE.21
‡In the secondary approach, costs of SREs were estimated based on inpatient and outpatient claims with diagnoses or procedure codes indicative of SREs among patients with newly diagnosed bone metastasis and 1 SRE and patients with any bone metastasis and ≥2 SREs, respectively.21
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.
Please see full Prescribing Information.
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..
