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Prior Authorization Protocol
XGEVATM (denosumab)

NATL

Interim Guidelines; Final Review and Approval by the P&T Committee Pending

Coverage of drugs is first determined by the memberís pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • Prevention of skeletal-related events in patients with bone metastases from solid tumors.
    • 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.
    • Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy
    • Xgeva is NOT indicated for the prevention of skeletal-related events in patients with multiple myeloma.
  2. Health Net Approved Indications and Usage Guidelines:
    • Diagnosis of bone metastases from solid tumors
    OR
    • Diagnosis of unresectable giant cell tumor of bone (GCTB) or where surgical resection is likely to result in severe morbidity
    OR
    • Diagnosis of hypercalcemia of malignancy (HCM) refractory to bisphosphonate therapy
  3. Coverage is Not Authorized For:
    • Prevention of skeletal-related events in patients with multiple myeloma
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and usage guidelines section unless there is sufficient documentation of efficacy and safety in the published literature.
  4. General Information:
    • In the Stopeck, et al study, mortality was higher with Xgeva in a subgroup analysis of patients with multiple myeloma (hazard ratio [95% CI] of 2.26 [1.13, 4.50]; n=180). Xgeva is currently being evaluated in a Phase 3 trial to determine its efficacy in patients with multiple myeloma in comparison to zoledronic acid.
    • According to the American Cancer Society, certain kinds of cancer (breast, prostate, lung, thyroid and kidney cancers) are more likely to spread to the bones.
    • Xgeva is undergoing evaluation for use in the treatment of several conditions associated with bone loss, including rheumatoid arthritis as well as to delay bone metastases and inhibit and treat bone destruction associated with cancer.
    • Results from the pivotal HALT study showed that male patients with non-metastatic prostate cancer undergoing androgen deprivation therapy treated with denosumab experienced a 62% reduction in the relative risk of suffering a new vertebral fracture with denosumab compared to placebo at 36 months. In May 2010, Europe Union approved Prolia for this indication.
    • Examples of unresectable GCTB would include sacral and spinal lesions and GCTB with pulmonary metastasis.
    • Examples where surgical excision of GCTB might result in severe morbidity would include surgery that would lead to joint resection, limb amputation or hemipelvectomy.
    • For the treatment of HCM, refractory to bisphosphonate therapy was defined in clinical trials as a corrected serum calcium (CSC) level >12.5 mg/dL despite IV bisphosphonate treatment within 7 to 30 days before receiving Xgeva.
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose
    zoledronic acid (Zometa)
    Hypercalcemia of Malignancy:
    4 mg IV; may repeat after a minimum of 7 days if serum calcium does not return to normal or remain normal after initial treatment
    Renal Dose Adjustment:
    Baseline CrCl = 50 to 60 mL/min; 3.5 mg IV
    Baseline CrCl = 40 to 49 mL/min; 3.3 mg IV
    Baseline CrCl = 30 to 39 mL/min: 3 mg IV

    This field intentionally left blank.

    ibandronate (Boniva)

    Hypercalcemia of Malignancy:
    2 - 6 mg IV over 1-2 hours

    This field intentionally left blank.

    pamidronate (Aredia)

    Moderate cancer-related hypercalcemia (corrected serum calcium: 12 to 13.5 mg/dL):
    60 - 90 mg IV over 2 to 24 hours
    Severe cancer-related hypercalcemia (corrected serum calcium: >13.5 mg/dL):
    90 mg IV over 2 to 24 hours

    This field intentionally left blank.

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Xgeva

    Bone Metastasis from Solid Tumors
    120 mg SC once every 4 weeks
    Administer calcium and vitamin D as
    necessary to treat or prevent hypocalcemia

    Giant Cell Tumor of Bone
    Initial dose (Day 1): 120 mg SC
    Second dose one week later (Day 8): 120 mg SC
    Third dose one week later (Day 15): 120 mg SC
    Maintenance: 120 mg SC every 4 weeks

    Hypercalcemia of Malignancy
    Initial dose (Day 1): 120 mg SC
    Second dose one week later (Day 8): 120 mg SC
    Third dose one week later (Day 15): 120 mg SC
    Maintenance: 120 mg SC every 4 weeks

    6 months or to member's renewal period, whichever is sooner.

  7. Product Availability:

    Injection: 120 mg/1.7 mL (70 mg/mL), single-use vial

  8. References:
    1. Xgeva [Prescribing information] Thousand Oaks, CA: Amgen. December 2014.
    2. American Cancer Society Bone Metastasis: Questions and Answers http://www.cancer.org/acs/groups/cid/documents/webcontent/003087-pdf.pdf. Accessed July 1, 2014.
    3. National Comprehensive Cancer Network. Bone Cancer Version 1.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. Accessed July 1, 2014.
    4. 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):5132-9.
    5. Smith MR, Egerdie B, Hernandez TN, et al. Denosumab in men receiving androgen deprivation therapy in non-metastatic prostate cancer. N Engl J Med. 2009;361:745-755.
    6. DrugDex Drug Database. Thompson Micromedex Web site. Available at: http://www.thomsonhc.com. Accessed January 26, 2015.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.