INDICATIONS
XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
XGEVA® is indicated for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
XGEVA® is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
Close Indication
Don’t let patients who are vulnerable to bone complications* go unprotected1
  • Overall survival in patients with metastatic cancer is increasing2-4
  • More than half of patients suffered a bone complication before starting treatment with a bone-targeting agent (retrospective analysis)5

*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.6

BONE METASTASES RISK

Patients with breast, prostate, or lung cancer are at the highest risk for developing bone metastases7-9*

7 out of 10 women with advanced metastatic breast cancer develop bone metastases
7 out of 10 men with advanced metastatic prostate cancer develop bone metastases
4 out of 10 patients with advancd metastatic lung cancer develop bone metastases

*Data represent the incidence of bone metastases based on autopsies of patients with cancer in select tumor types in which bone metastases are more prevalent.9

Bone metastases put patients at risk for bone complications10*

In a placebo arm of a radomized clinical trial 64% of women with breast cancer and bone metastases developed bone complications.

In the placebo arm of a radomized clinical trial 49% of men with prostate cancer and bone metastases developed bone complications.

*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.6

Data from the placebo arm (n=384) of a randomized trial evaluating the efficacy of an IV bisphosphonate in the reduction of bone complications in women with bone metastases from breast cancer.11

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.12

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BONE PAIN

Pain is a common symptom for your patients with bone metastases from solid tumors10

Bone metastases-related pain occurs frequently13

  • Pain is typically the first symptom of bone metastases14
  • 40% of patients reported significant levels of pain at diagnosis15

*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.6

BONE COMPLICATIONS* ARE STRONGLY ASSOCIATED WITH PAIN15

86% of patients with a bone complcation experienced bone pain

86% of patients with a bone complcation experienced bone pain

*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.6

The threat of bone complications may be present even if pain is not16

The same percentage of patients suffered 1 or more bone complications within 2 years whether or not they had bone pain at baseline16

  • From a retrospective analysis of patients with prostate cancer metastatic to the bone untreated with a bone-targeting agent
Percentage of patients who suffered 1 or more bone complications and bone pain

Data from the placebo arm (n=208) of a retrospective analysis evaluating the efficacy of an IV bisphosphonate in the reduction 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, surgery to bone, radiation to bone, spinal cord compression, and change in antineoplastic therapy to treat bone pain. One hundred ninety-one patients in the placebo arm had data capturing baseline pain.16

The same percentage of patients suffered 1 or more bone complications within 2 years whether or not they had bone pain at baseline16

  • From a retrospective analysis of patients with prostate cancer metastatic to the bone untreated with a bone-targeting agent

Data from the placebo arm (n=208) of a retrospective analysis evaluating the efficacy of an IV bisphosphonate in the reduction 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, surgery to bone, radiation to bone, spinal cord compression, and change in antineoplastic therapy to treat bone pain. One hundred ninety-one patients in the placebo arm had data capturing baseline pain.16

Percentage of patients who suffered 1 or more bone complications and bone pain

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THREAT OF BONE COMPLICATIONS

Patients with bone metastases from solid tumors are at risk for bone complications

Bone complications, also known as skeletal-related events (SREs), are defined as17,18:

Radiation to bone

Radiation to bone

  • Radiation to bone can require multiple treatments19-21
  • The most common reason for radiation is pain palliation; it is also used as prophylaxis for impending fracture or adjunct to surgery to reduce risk of bone complications20,22
  • A common schedule of radiation is 10 treatments over 2 weeks19-21

The NCCN® Bone Health in Cancer Care task force has categorized the need for palliative radiation to the bone as one of several possible skeletal-related events1*

*Skeletal-related events (SREs) are defined as the need for radiation to bone, pathologic fracture, need for surgery to bone, and spinal cord compression.6

National Comprehensive Cancer Network® (NCCN®).

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Pathologic fracture

Pathologic fracture

  • Pathologic fractures can be painful for patients and often do not heal, resulting in bone destruction23
  • Pathologic fractures occur most commonly in the ribs, vertebrae, pelvis, and femur9,24
  • Fractures of weight-bearing bones often require surgical stabilization25
Surgery to bone

Surgery to bone

  • Surgery to bone may be required to treat pain, pathologic fracture, or other complications23,25
  • Postsurgical rehabilitation may be required26
Spinal cord compression

Spinal cord compression

  • Spinal cord compression is considered an oncologic emergency27
  • The most common tumor types associated with spinal cord compression are28,29:
    • Breast (20%-30%)
    • Lung (15%)
    • Prostate (10%-15%)

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ONSET OF BONE COMPLICATIONS

Many patients with solid tumors are at immediate risk for bone complications*

An analysis of 47,052 bone-targeting agent-naïve patients, including breast, prostate, or lung cancer, found that bone complications often occur within the first few months of bone metastases diagnosis30

Within 1 month, 1 out of 4 patients suffered a bone complication. / Within 3 months, 1 out of 3 patients suffered a bone complication.

Prescribing data estimated that more than half of the 330,000 patients living with bone metastases were not receiving treatment with a bone-targeting agent (retrospective analysis)5

Within 1 month, 1 out of 4 patients suffered a bone complication. / Within 3 months, 1 out of 3 patients suffered a bone complication.

Prescribing data estimated that more than half of the 330,000 patients living with bone metastases were not receiving treatment with a bone-targeting agent (retrospective analysis)5

*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.6

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. 13% of patients had at least one SRE prior to bone metastases diagnosis.30

The risk of bone complications continues to increase for those with breast, prostate, or lung cancer over time30

Proportion of Patients with at least one bone complication over time by tumor type
Proportion of Patients with at least one bone complication over time by tumor type


Almost half (46%) of patients fell victim to a bone complication within a year of bone metastases diagnosis, regardless of prior bone complication status30


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. 13% of patients had at least one SRE prior to bone metastases diagnosis.30

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SUBSEQUENT BONE COMPLICATIONS

A prior bone complication* can markedly increase the risk for developing a subsequent bone complication in patients with solid tumors30

Risk of bone complications for patients with or without a bone complication at baseline
Risk of bone complications for patients with or without a bone complication at baseline


In another study of prostate cancer patients who had subsequent bone complication, 55% had a bone complication of a different type31†


*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.6

Based on a SEER-Medicare linked analysis of 2,619 prostate cancer patients who experienced a subsequent SRE.31

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. 13% of patients had at least one SRE prior to bone metastases diagnosis.30

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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.

The most common adverse reactions in patients receiving XGEVA® for giant cell tumor of bone were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis. The most common adverse reactions resulting in discontinuation of XGEVA® were osteonecrosis of the jaw and tooth abscess or tooth infection.

The most common adverse reactions in patients receiving XGEVA® for hypercalcemia of malignancy were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Indications

XGEVA® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.

XGEVA® is indicated for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

XGEVA® is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

Please see Full Prescribing Information.

 

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.

References

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  23. Wedin R. Surgical treatment for pathologic fracture. Acta Orthop Scand Suppl. 2001;72(suppl 302):1-29.
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  25. Moore RE, Lackman RD. Metastatic bone disease. UPOJ. 2010;20:117-120.
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