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09-J1000-25

Original Effective Date: 08/15/10

Reviewed: 01/11/17

Revised: 02/15/17

Next Review: 01/10/18

Subject: Denosumab (Prolia™; Xgeva™) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Dosage/ Administration Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Denosumab (Prolia™, Xgeva™) is a fully human monoclonal antibody against receptor activator of nuclear factor κ-β ligand (RANKL) and inhibits its action on the surface receptors expressed on osteoclasts. This causes reduced osteoclast formation, function and survival, consequently decreasing bone resorption, increasing bone mass, and strengthening both cortical and trabecular bone. The role of excessive RANKL as a contributor to conditions characterized by bone loss or bone destruction has been well studied. A comprehensive clinical development program for denosumab resulted in a robust data set that supported global and regulatory approvals of the RANKL-targeted antibody denosumab in the bone loss and cancer inducted bone destruction settings.

About 10 million Americans (80% who are women) are estimated to have osteoporosis. In women over 50, one out of two will have an osteoporosis-related fracture in their remaining lifetime leading to significant healthcare costs. A T-score based on a dual energy x-ray (DXA) measurement is used to classify patients as being normal (-1 or more), having osteopenia (-1 to -2.5), or having osteoporosis (-2.5 or less). Denosumab was initially approved (as Prolia) by the FDA in June 2010 for the treatment of osteoporosis in postmenopausal women who are at high risk for fracture or have failed or did not tolerate other treatment. The initial approval was expanded to include the treatment of men at high risk for fractures, osteoporosis prophylaxis in women at high risk for bone fractures after receiving adjuvant aromatase inhibitor therapy for breast cancer, and osteoporosis prophylaxis in men at high risk for bone fractures after receiving androgen deprivation therapy for non-metastatic prostate cancer. Denosumab (as Xgeva) was approved in 2010 for the prevention of skeletal-related events (SRE) in individuals with bone metastases from solid tumors but does not include use in patients with multiple myeloma. Denosumab (as Xgeva) is also approved for the treatment of hypercalcemia of malignancy and treatment of giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

There are limited head-to-head studies comparing denosumab to other agents for osteoporosis prophylaxis in men (secondary to androgen deprivation therapy) or women (secondary to aromatase inhibitor therapy). However, data from a meta-analysis of four randomized, double-blind, controlled clinical trials including the Determining Efficacy: comparison of initiation denosumab versus alendronate (DECIDE) trial, showed no significant difference in fracture risk reduction between denosumab and alendronate (44 vs. 24 events, respectively; odds ratio 1.42, 95% CI 0.84 to 2.4, p=0.19), although denosumab was associated with greater increases in bone mineral density (BMD). All studies enrolled postmenopausal women aged 60.3 to 68.2 years who had low bone mass (all T-scores between -1.4 to 2.6). Omitting any single trial from analysis did not influence the fracture risk reduction outcomes and heterogeneity was not significant across the studies.

In individuals with advanced cancer, bone metastases can have significant clinical consequences such as bone pain, pathological fractures, or spinal cord compression that may result in physical and functional impairment, and increased mortality. Intravenous bisphosphonates, predominantly zoledronic acid (Zometa), are effective at reducing SREs. Several well-designed clinical studies have evaluated the efficacy of denosumab versus zoledronic acid in individuals with bone metastases secondary to solid tumors. In a phase 3 double-blind, double-dummy, non-inferiority trial, subjects with advanced breast cancer and bone metastases were equally randomized to denosumab 120 mg subcutaneously (SQ) or zoledronic acid 4 mg intravenously (IV) every four weeks and stratified according to history of previous SRE, treatment with chemotherapy prior to randomization, prior oral bisphosphonate therapy, and region. The primary outcome was the time to first SRE. Subjects treated with denosumab had an 18% reduction in the risk of first SRE when compared to subjected treated with zoledronic acid, demonstrating both the non-inferiority and superiority of denosumab therapy when compared to zoledronic acid (p<0.001 for non-inferiority, and p=0.01 for superiority). In a similarly designed study, denosumab was superior to zoledronic acid for delay of time to first SRE by 3.6 months in men with bone metastases from castrate-resistant prostate cancer. In a subset of patients with bone metastases from lung cancer, an improved median overall survival was demonstrated with denosumab as compared to zoledronic acid (9.5 versus 8 months; hazard ratio 0.78). Although denosumab was superior to zoledronic acid in the settings of breast cancer, prostate cancer and lung cancer, it was not superior when compared to zoledronic acid in subjects with other solid tumors. In an international, randomized, double-blind, double-dummy non-inferiority trial, adults with solid tumors other than breast and castrate-resistant prostate cancer with bone metastases were randomized to 120 mg denosumab SQ or 4 mg zoledronic acid IV. Denosumab demonstrated non-inferiority to zoledronic acid in the time to first SRE, but the difference was not statistically significantly different in the superiority analysis (20.6 months vs. 16.3 months, respectively; HR 0.84, 95% CI 0.71-0.98, p<0.001 for non-inferiority; p=0.06 for superiority).

POSITION STATEMENT:

I. Initiation of denosumab (Prolia™, Xgeva™) meets the definition of medical necessity when administered for the treatment of the indications in Table 1 when ALL of the indication-specific criteria are met:

Table 1

Indications and Specific Criteria

Indication

Criteria

Prolia (duration of approval: 1 year)

Postmenopausal Osteoporosis or Osteoporosis in biological males

When ALL of the following are met:

1. Member meets ONE of the following:

a. Diagnosed with osteoporosis defined as a pre-treatment bone mineral density (BMD) T-score -2.5 or lower*

b. Member has a history of osteoporotic hip or vertebral fracture

2. The dose does not exceed 60 mg SQ every 6 months

3. EITHER of the following:

a. Member has tried and failed bisphosphonate therapy (oral or IV)

b. Member has a contraindication or intolerance to both oral and IV bisphosphonate therapy

Non-metastatic Prostate Cancer-Increase bone mass

When ALL of the following are met:

1. Member is diagnosed with non-metastatic prostate cancer

2. Member is receiving androgen deprivation therapy (e.g., surgical castration, medical castration, gonadotropin-releasing hormone agonist)

3. Member meets ONE of the following:

a. Pre-treatment BMD T-score of -1 or lower*

b. Member has a history of osteoporotic hip or vertebral fracture

4. The dose does not exceed 60 mg SQ every 6 months

Breast Cancer-Increase bone mass

When ALL of the following are met:

1. Member is diagnosed with hormone-receptor positive breast cancer

2. Member is receiving concomitant aromatase inhibitor therapy (e.g., anastrozole [Arimidex], letrozole [Femara], exemestane [Aromasin]) as adjuvant therapy

3. Dose does not exceed 60 mg SQ every 6 months

4. EITHER of the following:

a. Member has tried and failed† bisphosphonate therapy (oral or IV)

b. Member has a contraindication or intolerance to both oral and IV bisphosphonate therapy

Xgeva (duration of approval: 180 days)

Bone metastases secondary to breast cancer

When ALL of the following are met:

1. Member is diagnosed with breast cancer

2. Member has bone metastases

3. Member has a life expectancy of 3 or more months

4. Denosumab will be used in conjunction with standard antineoplastic therapy (i.e., chemotherapy or endocrine therapy)

5. Dose does not exceed 120 mg SQ every 4 weeks

Bone metastases secondary to lung cancer

When ALL of the following are met:

1. Member is diagnosed with lung cancer

2. Member has bone metastases

3. Dose does not exceed 120 mg SQ every 4 weeks.

Bone metastases secondary to castrate-recurrent prostate cancer

When ALL of the following are met:

1. Member is diagnosed with castrate-recurrent prostate cancer

2. Member has bone metastases

3. Dose does not exceed 120 mg SQ every 4 weeks.

Bone metastases secondary to solid tumor (other than breast cancer, castrate-recurrent prostate cancer, or lung cancer)

When ALL of the following are met:

1. Member has a solid tumor cancer diagnosis (e.g., thyroid cancer, kidney cancer)

2. Denosumab is not used for bone metastases secondary to multiple myeloma

3. Member has tried/failed or has a contraindication/intolerance to zoledronic acid (Zometa®)

4. Member has bone metastases

5. Dose does not exceed 120 mg SQ every 4 weeks.

Giant Cell Tumor of the Bone

When BOTH of the following are met:

1. Denosumab is used as a single agent or in combination with one of the following

a. interferon alfa

b. radiation therapy

2. Dose does not exceed 120 mg every 4 weeks (Note: an additional dose of 120 mg on days 8 and 15 will be permitted for the first cycle only)

Hypercalcemia of Malignancy

When BOTH of the following are met:

1. Member has a cancer diagnosis with tumor related hypercalcemia (albumin corrected calcium± of 12 mg/dL or greater)

2. Member has tried and failed or has a contraindication/intolerance to intravenous bisphosphate therapy (e.g., zoledronic acid)

3. Dose does not exceed 120 mg every 4 weeks (Note: an additional dose of 120 mg on days 8 and 15 will be permitted for the first cycle only)

BMD, bone mineral density; IV, intravenous

*Measured at the femoral neck, total hip, lumbar spine, or 33% radius

Failure is defined as a new fracture in a compliant member or significant loss of bone mineral density on follow-up scans.

II. Continuation of denosumab meets the definition of medical necessity for the indications in Table 1 when ALL of the following are met

a. Member has a history of beneficial response to therapy

b. The member has been previously approved by Florida Blue or another health plan in the past 2 years, OR the member has previously met all indication-specific criteria for coverage

c. The dose does not exceed the following

1. Prolia: 60 mg every 6 months

2. Xgeva: 120 mg every 4 weeks

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

Table 2

FDA-approved indications and dosage

Indication

Dose/Administration

Prolia

Treatment of postmenopausal women with osteoporosis at high risk for fracture

• 60 mg SQ every 6 months

• Inject into upper arm, upper thigh, or abdomen

• Concomitant therapy with calcium 1000 mg and at least 400 IU vitamin daily is recommended

Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer

Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Xgeva

Prevention of skeletal-related events due to bone metastases from solid tumors

• 120 mg SQ every 4 weeks

• Inject into upper arm, upper thigh, or abdomen

• Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia

Giant cell tumor of bone

• 120 mg every 4 weeks with additional 120 mg doses on days 8 and 15 of the first cycle.

• Inject into upper arm, upper thigh, or abdomen

• Concomitant therapy with calcium and vitamin D as necessary to treat or prevent hypocalcemia

Hypercalcemia of malignancy

• 120 mg every 4 weeks with additional 120 mg doses on days 8 and 15 of the first cycle.

• Inject into upper arm, upper thigh, or abdomen

SQ; subcutaneously

NOTE: Xgeva is not indicated for the prevention of skeletal related events in individuals with multiple myeloma.

Dose Adjustments

Renal Impairment: dosage adjustments are not required for members with renal impairment. In clinical studies, subjects treated with denosumab with severe renal impairment (creatinine clearance less than 30 mL/min) or receiving dialysis were at greater risk of developing hypocalcemia. Clinical monitoring of calcium, phosphorus, and magnesium is highly recommended and adequate intake of calcium and vitamin D is important.

Hepatic Impairment: clinical studies have not been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of denosumab.

Drug Availability

Prolia: single-use prefilled syringe containing 60 mg in a 1 mL solution and single-use vial containing 60 mg in a 1 mL solution.

Xgeva: single-use vial containing 120 mg/1.7 mL (70 mg/mL)

PRECAUTIONS:

CONTRAINDICATIONS:

Prolia and Xgeva

Hypocalcemia: correct prior to initiating; treatment with denosumab may exacerbate hypocalcemia, especially in members with renal impairment. Members treated with denosumab should receive adequate calcium and vitamin D supplementation.

Hypersensitivity: do not administer to members with a history of systemic hypersensitivity to any component of the product.

Prolia

Pregnancy: Prolia is classified as Pregnancy Category X and may cause fetal harm when administered to pregnant women based on findings in animals. Of note, Xgeva is classified as Pregnancy Category D, but also caused fetal harm when administered to pregnant women based on findings in animals.

WARNINGS:

Prolia and Xgeva

Patients receiving Prolia should not receive Xgeva and vice-versa.

Hypersensitivity: anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs.

Hypocalcemia: decreases in serum calcium levels (less than 8.5 mg/dL) were reported in 0.4% of women in placebo group vs. 1.7% of women in the denosumab group at one month (number needed to harm=77). The nadir in serum calcium level occurs approximately 10 days after administration. Use caution in members who are predisposed to hypocalcemia and disturbances of mineral metabolism including patients with a history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of the small intestine, severe renal impairment (CrCl <30 mL/min), or dialysis. Clinical monitoring of calcium, phosphorus, and magnesium is highly recommended. Encourage daily supplements of calcium and vitamin D.

Osteonecrosis of the jaw: has been reported by individuals treated with denosumab; monitor members for symptoms.

Atypical femoral fractures: have been reported by individuals treated with denosumab; evaluate members with thigh or groin pain to rule out a femoral fracture.

Prolia

Serious infections: may occur, including those leading to hospitalization. Members should be advised to seek prompt medical attention if they develop signs or symptoms of infection, including skin infections (e.g., cellulitis).

Dermatologic reactions: dermatitis, rashes, and eczema have been reported. Consider discontinuing therapy if severe symptoms develop.

Severe Bone, Joint Muscle Pain: Discontinue if severe symptoms develop.

Suppression of bone turnover: significant suppression has been demonstrated; monitor members for consequences of bone over-suppression.

Xgeva

Embryo-Fetal Toxicity: can cause fetal harm. Advise females of the potential risk to fetus and use highly effective contraception.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J0897

Injection, denosumab, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity for Prolia™: (Effective 10/01/15)

C50.011 – C50.929

Malignant neoplasm of breast

C61

Malignant neoplasm of prostate

M80.00XA – M80.00XS
M80.011A – M80.011S

M80.012A – M80.012S

M80.019A – M80.019S
M80.021A – M80.021S
M80.022A – M80.022S

M80.029A – M80
.029S
M80.031A – M80.031S
M80.032A – M80.032S
M80.039A – M80.039S
M80.041A – M80.041S
M80.042A – M80.042S
M80.049A – M80
.049S
M80.051A – M80.051S
M80.052A – M80.052S
M80.059A – M80.059S
M80.061A – M80.061S
M80.062A – M80.062S
M80.069A – M80.069S

M80.071A –
M80.071S
M80.072A – M80.072S
M80.079A – M80.079S

M80.08XA – M80.08XS

Age-related osteoporosis with current pathological fracture

M80.80XA – M80.80XS
M80.811A – M80.811S
M80.812A – M80.812S
M80.819A – M80.819S
M80.821A – M80.821S
M80.822A – M80.822S

M80.8
29A – M80.829S
M80.831A – M80.831S
M80.832A – M80.832S
M80.839A – M80.839S
M80.841A – M80.841S
M80.842A – M80.842S
M80.8
49A – M80.849S
M80.851A – M80.851S
M80.852A – M80.852S
M80.859A – M80.859S
M80.861A – M80.861S
M80.862A – M80.862S
M80.869A – M80.869S

M
80.871A – M80.871S
M80.872A – M80.872S
M80.879A – M80.879S

M80.88XA – M80.88XS

Other osteoporosis with current pathological fracture

M81.0

Age-related osteoporosis without current pathological fracture

M81.6

Localized osteoporosis (Lequesne)

M81.8

Other osteoporosis without current pathological fracture

M89.9

Disorder of bone, unspecified

M94.9

Disorder of cartilage, unspecified

N95.1

Menopausal and female climacteric states

T38.6X5A – T38.6X5S

Adverse effect of antigonadotrophins, antiestrogens, antiandrogens, not elsewhere classified

T38.7X5A – T38.7X5S

Adverse effect of androgens and anabolic congeners

Z78.0

Asymptomatic menopausal state

Z79.811

Long term (current) use of aromatase inhibitors

Z79.818

Long term (current) use of other agents affecting estrogen receptors and estrogen levels

ICD-10 Diagnoses Codes That Support Medical Necessity for Xgeva™: (Effective 10/01/15)

C33

Malignant neoplasm of trachea

C34.00 – C34.02

Malignant neoplasm of unspecified main bronchus

C34.10 – C34.12

Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.2

Malignant neoplasm of middle lobe, bronchus or lung

C34.30 – C34.32

Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.80 – C34.82

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.90 – C34.92

Malignant neoplasm of unspecified part of unspecified bronchus or lung

C40.00 – C40.92

Malignant neoplasm of bone and articular cartilage of limbs

C41.0 – C41.9

Malignant neoplasm of bone and articular cartilage of other and unspecified sites

C50.011 – C50.929

Malignant neoplasm of breast

C61

Malignant neoplasm of prostate

C64.1 C64.9

Malignant neoplasm of unspecified kidney, except renal pelvis

C65.1 C65.9

Malignant neoplasm of unspecified renal pelvis

C73

Malignant neoplasm of thyroid gland

C79.51 – C79.52

Secondary malignant neoplasm of bone and bone marrow

D48.0

Neoplasm of uncertain behavior of bone and articular cartilage

E83.52

Hypercalcemia

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) WAS found at the time of the last guideline revised date. The following Local Coverage Determination (LCD) was reviewed on the last guideline revised date: Bisphosphonates (intravenous (IV)) and Monoclonal Antibodies in the Treatment of Osteoporosis and Their Other Indications, (L33270) located at fcso.com.

DEFINITIONS:

Adjuvant Treatment: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will return. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biologic therapy. Adjuvant therapy can be used after or in combination with another form of cancer therapy and is commonly used following removal of a cancerous tumor to further help in treatment.

Androgen deprivation: loss or absence of androgen.

Metastatic cancer: when cancer spreads from the primary site (place where it started) to other places in the body.

Multiple myeloma: a disseminated type of plasma cell dyscrasia characterized by multiple bone marrow tumor foci

Osteopenia: reduced bone mass due to the decrease in the rate of osteoid synthesis to a level insufficient to compensate normal bone lysis. The World Health Organization (WHO) defines osteopenia as a T-score at the femoral neck of between –1.0 SD and –2.5 SD below the young female adult mean.

Osteoporosis: Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density (BMD) value for the hip, spine, or wrist of 2.5 standard deviations (SD) or more below the mean for healthy young white women, or a T-score of less than or equal to – 2.5. The disease is characterized by an increased risk of fractures, which can result in pain, diminished quality of life, decreased physical mobility and independence, inability to work, and increased burden on caregivers.

RANKL (Receptor Activator for Nuclear Factor κ B Ligand): also known as TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and ODF (osteoclast differentiation factor), is a molecule important in bone metabolism. This natural and necessary surface-bound molecule found on osteoblasts serves to activate osteoclasts, which are the cells involved in bone resorption. Overproduction of RANKL is implicated in a variety of degenerative bone diseases, such as rheumatoid arthritis and psoriatic arthritis.

Risk Factors for Osteoporosis: For osteoporotic fractures, includes low BMD, parental history of hip fracture, low body weight, previous fracture, smoking, excess alcohol intake, glucocorticoid use, secondary osteoporosis (e.g., rheumatoid arthritis) and history of falls. These readily accessible and commonplace factors are associated with the risk of hip fracture and, in most cases, with that of vertebral and other types of fracture as well.

RELATED GUIDELINES:

Bone Mineral Density Studies, 04-70000-21
Ibandronate IV (Boniva®), 09-J0000-71

Percutaneous Vertebroplasty, Kyphoplasty and Sacroplasty, 02-20000-18

Teriparatide (Forteo®), 09-J0000-47

Zoledronic Acid IV (Reclast®; Zometa®), 09-J0000-72

OTHER:

None applicable.

REFERENCES:

  1. ACOG Practice Bulletin on Osteoporosis. American Family Physician. 2013; 88(4): 273 – 275.
  2. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis. Endocr Pract. 2016; 22: Suppl 4;1-42.
  3. Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumor of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 2013:14:901-08.
  4. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2016. URL www.clinicalpharmacilogy-ip.com Accessed 12/16/16.
  5. Cohen SB, Dore RK, Lane NE, et al. Denosumab Treatment Effects on Structural Damage, Bone Mineral Density, and Bone Turnover in Rheumatoid Arthritis. Arthritis Rheum 2008;58:1299-1309.
  6. Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014; 25 (10): 2359-81.
  7. Cummins SR, San Martin J, McClung MR, et al. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engl J Med 2009;361:756-65.
  8. Denosumab. In: McEvoy GK, editor. AHFS drug information 2016[monograph on the Internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2016 [cited 2016 Dec 16]. Available from: http://online.statref.com. Subscription required to view
  9. Ellis GK, Bone HG, Chlebowski, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 26:4875-82.
  10. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 12/16/16.
  11. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 12/27/16.
  12. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 2.2017. Bone Cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/bone.pdf Accessed 12/27/16.
  13. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 2.2016. Breast Cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf Accessed 12/27/16.
  14. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 2.2017. Kidney cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf Accessed 12/27/16.
  15. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 3.2017. Non-small cell lung cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf Accessed 12/27/16.
  16. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2017. Prostate Cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf Accessed 12/27/16.
  17. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2016. Thyroid Cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/thyroid.pdf Accessed 12/27/16.
  18. North American Menopause Society (NAMS) Position Statement. Management of osteoporosis in postmenopausal women: 2010 position statement of the NAMS. Menopause. 2010; 17(1): 25-54.
  19. NOF: fast facts on osteoporosis [Internet]. Washington DC: National Osteoporosis Foundation; c2010 [cited 2012 Dec 3]. Available from: http://www.NOF.org.
  20. Prolia (denosumab) [package insert]. Amgen Inc. Thousand Oaks (CA): August 2016
  21. Scagliotti GV, Hirsh V, Siena S, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid; a subgroup analysis from a randomized phase 3 study. J Thorac Oncol 2012;7:1823-29.
  22. Smith MR, Egerdie B, Toriz NH, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745-55.
  23. Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advance breast cancer: a randomized, double-blind study. J Clin Oncol 2010.
  24. Watts NB, Adler RA, Bilezikan JP, Drake MT, et al. Osteoporosis in men: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2012;97(6):1802-22.
  25. Watts NB, Bilezkian JP, Camacho PM et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocrine Practice. 2010; 16 (Suppl 3): 1-37.
  26. Xgeva (denosumab) [package insert]: Ament Inc. Thousand Oaks (CA): March 2016.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 01/11/17.

GUIDELINE UPDATE INFORMATION:

08/15/10

New Pharmacy Coverage Guideline.

11/15/10

Revision to guideline; consisting of modifying coverage criteria.

02/15/11

Revision to guideline; consisting of new brand name, new indication, update dosing, coding and references.

05/15/11

Review and revision to guideline; consisting of updating references.

08/17/11

Revision; ICD-10 codes updated.

11/15/11

Revision to guideline; consisting of adding two new FDA-approved indications to Position Statement.

01/01/12

Revision to guideline; consisting of modifying position statement and coding update.

05/15/12

Review and revision to guideline; consisting of updating position statement and coding.

09/15/12

Revision to guideline; consisting of updating position statement.

02/15/13

Review and revision to guideline; consisting of revising/reformatting position statement, dosage/administration section, precautions section; updated references; added definitions.

09/15/13

Revision to guideline; consisting of administrative action to remove requirement of high risk for fracture from position statement and add approval duration.

02/15/14

Review and revision to guideline; consisting of revising position statement to include new FDA-approved indication, updating dosage/administration, precautions, references, and coding.

02/15/15

Review and revision to guideline; consisting of revising position statement, updating dosage/administration, references.

10/01/15

Revision consisting of update to Program Exceptions section.

11/01/15

Revision: ICD-9 Codes deleted.

02/15/16

Review and revision to guideline; consisting of revising position statement, updating description, precautions, coding and references.

12/15/16

Review and revision to guideline; consisting of updating position statement and references.

02/15/17

Review and revision to guideline; consisting of updating position statement and references.

Date Printed: October 20, 2017: 08:40 AM