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.
  • Study schema

    Evaluated in 3 identically designed head-to-head studies vs ZA + 2-year OLE phase 2,3 group-5

    StudySchema_graph

    OLE, open-label extension.

  • Select demographics and baseline characteristics

    From the prespecified integrated analysis of 3 pivotal studies 1,2,4-6

    Baseline characteristics XGEVA®
    (n=2,862)
    ZA
    (n=2,861)
    Median age, years 63 63
    ECOG status 0-1, % 90 89
    Creatinine clearance ≥30 and
    ≤60 mL/mina, %
    17 17
    Presence of visceral metastases, % 42 40
    Prior bone complication, % 39 40
    Primary tumor typeb, % XGEVA®
    (n=2,862)
    ZA
    (n=2,861)
    Breast 36 36
    Prostate 33 33
    Non-small cell lung 12 12
    Multiple myeloma 3 3
    Renal 2 2
    Small cell lung 2 2
    Other 11 10

    aPatients with creatinine clearance <30 mL/min were excluded from XGEVA® pivotal trials. 1

    bBased on randomization; total may not equal 100% due to rounding. 2

    ECOG, Eastern Cooperative Oncology Group.

  • Breast cancer with bone metastases trial data

    In women with breast cancer and bone metastases

    XGEVA® prevented bone complications for >2 years 1,7

    group-9breast_cancer_graph

    riskreduction_za3 riskreduction_za5

    NCCN Clinical Practice Guidelines (NCCN Guidelines®)

    Denosumab (XGEVA® Q4W) is a Category 1 recommended option for the prevention of bone complications in women with breast cancer and bone metastases 8

    Category 1: Based on high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. 8

  • Prostate cancer with bone metastases trial data

    In prostate cancer patients with bone metastases

    XGEVA® prevented bone complications for a median of 20.7 months 1,9

    group-7prostate_cancer_graph

    riskreduction_za5 riskreduction_za5
    NCCN Guidelines®

    Denosumab (XGEVA® Q4W) is the only Category 1 Preferred bone-targeting agent for men with prostate cancer and bone metastases 10

    Category 1: Based on high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. 10

BREAST CANCER AND BONE METASTASES

with Dr. Francis Arena and Dr. Noam Drazin

“For the best chance of achieving results like those seen in the phase 3 clinical trials, dose your patients every 4 weeks.”

—Dr. Francis Arena

PROSTATE CANCER AND BONE METASTASES

with Dr. Neal Shore and Dr. Jorge Garcia

“In a head-to-head phase 3 trial, XGEVA® was superior to zoledronic acid.”

—Dr. Jorge Garcia

2.1_Clinical_ExpertInsight_FrancisArena
BREAST CANCER
1.2_About_Risk_PC
PROSTATE CANCER

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. 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.

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.

 

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. Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be..

References:

  1. XGEVA® (denosumab) prescribing information, Amgen.
  2. Lipton A, Fizazi K, Stopeck AT, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012;48(16):3082-3092.
  3. Stopeck AT, Fizazi K, Body JJ, et al. Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer. Support Care Cancer. 2016;24(1):447-455.
  4. Data on file, Amgen; [1]; 2010.
  5. Data on file, Amgen; [2]; 2010.
  6. Data on file, Amgen; 2009.
  7. Stopeck AT, Lipton A, Body J-J, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132-5139.
  8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.6.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed August 25, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 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.
  9. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study. Lancet. 2011;377(9768):813-822.
  10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed August 25, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 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.
  11. Cleeland CS, Body J-J, Egerdie B, et al. Pain outcomes in patients with advanced breast cancer and bone metastases. Cancer. 2013;119(4):832-838.
  12. Brown JE, Cleeland C, Fallowfield L, et al. Pain outcomes in patients with bone metastases from castrate-resistant prostate cancer: results from a phase 3 trial of denosumab vs zoledronic acid. Poster presented at: 26th Annual EAU Congress; March 18-22, 2011; Vienna, Austria. Abstract 1091.
  13. Henry D, Vadhan-Raj S, Hirsh V, et al. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer. 2014;22(3):679-687.
  14. Cleeland CS. The measurement of pain from metastatic bone disease: capturing the patient’s experience. Clin Cancer Res. 2006;12(20 Pt 2):6236s-6242s.