Clinical UM Guideline

 

Subject: Denosumab (Prolia®, Xgeva®)
Guideline #: CG-DRUG-73 Publish Date:    12/27/2017
Status: New Last Review Date:    11/02/2017

Description

This document addresses the use of denosumab for the treatment of individuals with osteoporosis, treatment induced bone loss, bone metastases, giant cell tumor of the bone, hypercalcemia of malignancy and for all other indications, including multiple myeloma and rheumatoid arthritis which are currently being studied. Denosumab (Prolia, Xgeva; Amgen Inc., Thousand Oaks, CA) is a subcutaneous, fully human monoclonal antibody that is specifically designed to target the human receptor activator of nuclear factor kappa-B ligand (RANKL).

Clinical Indications

Medically Necessary:

Denosumab (Prolia)

Denosumab (Prolia) is considered medically necessary for the treatment of postmenopausal adult (greater than or equal to 18 years of age) women or adult men with osteoporosis (defined as a T score -2.5 or less) who meet criterion A, B, or C below:

  1. Individual has had at least one osteoporotic (minimal trauma) fracture; or
  2. Individual has two or more of the following risk factors for osteoporotic fracture:
    1. hypogonadism or premature ovarian failure
    2. low body mass
    3. smoking
    4. rheumatoid arthritis
    5. alcohol intake of 3 or more drinks/day
    6. vitamin D deficiency
    7. low calcium intake
    8. hyperkyphosis
    9. parental hip fracture
    10. multiple falls
    11. medication: anticoagulants, anticonvulsants, aromatase inhibitors, cancer chemotherapeutic drugs, gonadotropin-releasing hormone agonists, (glucocorticoid daily dosage equivalent to 5mg or greater of prednisone for at least 3 months); or
  3. Individual has failed, is intolerant to or has a medical contraindication to other available osteoporosis therapies (for example, bisphosphonates).

Denosumab (Prolia) is considered medically necessary as a treatment of bone loss for adult women receiving adjuvant aromatase inhibitor therapy for breast cancer or adult men receiving androgen deprivation therapy for non-metastatic prostate cancer who meet criterion A or B below:

  1. Individual has had at least one osteoporotic (minimal trauma) fracture; or
  2. Individual has one or more of the following additional risk factors for osteoporotic fracture:
    1. low body mass
    2. smoking
    3. rheumatoid arthritis
    4. alcohol intake of 3 or more drinks/day
    5. vitamin D deficiency
    6. low calcium intake
    7. hyperkyphosis
    8. parental hip fracture
    9. multiple falls
    10. medication: anticoagulants, anticonvulsants, (glucocorticoid daily dosage equivalent to 5mg or greater of prednisone for at least 3 months).

Denosumab (Xgeva)

Denosumab (Xgeva) is considered medically necessary when used for the prevention of skeletal-related events in adults (greater than or equal to 18 years of age) with solid tumor bone metastases (excluding prostate cancer unless castration resistant/recurrent).

Denosumab (Xgeva) is considered medically necessary for the treatment of hypercalcemia of malignancy, defined as an albumin-corrected serum calcium level greater than 12.5 mg/dL (3.1 mmol/L), when both of the following criteria below are met:

  1. Adults (greater than or equal to 18 years of age); and
  2. Refractory to recent (within last 30 days) treatment with intravenous bisphosphonate therapy (for example, pamidronate, zoledronic acid).

Denosumab (Xgeva) is considered medically necessary for the treatment of localized or metastatic giant cell tumor of the bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity when either of the following criteria below are met:

  1. Adults (greater than or equal to 18 years of age); or
  2. Skeletally mature adolescents (defined by at least one mature long bone [for example; closed epiphyseal growth plate of the humerus]).

Not Medically Necessary:

Denosumab (Prolia) is considered not medically necessary for all other indications not listed above as medically necessary or when the criteria specified above are not met.

Denosumab (Xgeva) is considered not medically necessary for the prevention of skeletal-related events in individuals with multiple myeloma.

Denosumab (Xgeva) is considered not medically necessary when all of the criteria specified above are not met, for presence of uncorrected pre-existing hypocalcemia or for the treatment of all other indications.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

 

J0897

Injection, denosumab, 1 mg [Prolia, Xgeva]

 

 

 

ICD-10 Diagnosis

 

C00.0-C39.9

Malignant neoplasms 

C40.00-C41.9

Malignant neoplasm of bone and articular cartilage

C43.0-C60.9

Malignant neoplasms

C61

Malignant neoplasm of prostate

C62.00-C75.9

Malignant neoplasms

C76.0-C76.8

Malignant neoplasm of other and ill-defined sites

C79.51

Secondary malignant neoplasm of bone

D48.0

Neoplasm of uncertain behavior of bone and articular cartilage [specified as GCTB]

E83.52

Hypercalcemia

M81.0-M81.8

Osteoporosis without current pathological fracture

M85.80-M85.9

Other specified disorders of bone density and structure [osteopenia]

N95.1

Menopausal and female climacteric states

Z08

Encounter for follow-up examination after completed treatment for malignant neoplasm

Z51.11-Z51.12

Encounter for antineoplastic chemotherapy and immunotherapy

Z79.51-Z79.52

Long term (current) use of steroids

Z79.811

Long term (current) use of aromatase inhibitors

Z79.899

Other long term (current) drug therapy [prophylactic drug therapy]

Z85.00-Z85.45

Personal history of malignant neoplasms

Z85.46

Personal history of malignant neoplasm of prostate

Z85.47-Z85.59

Personal history of malignant neoplasms

Z85.810-Z85.9

Personal history of malignant neoplasms 

Z87.310

Personal history of (healed) osteoporosis fracture

Discussion/General Information

Denosumab (Prolia, Xgeva) is designed to bind to RANKL, a protein that acts as the primary signal to promote bone resorption. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. Prolia was originally approved in 2010, by the U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Subsequently, the FDA approved additional specific indications for treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer and treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer (Product Information Label, 2017).

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (2014), more than 53 million people in the United States today either have osteoporosis or are at high risk for the disease as a result of low bone mass. Osteoporosis is a disease in which the bones become weak and are more likely to break. The disease is 4 times more likely to occur in women than in men. A total of 1.5 million fractures occurring annually, 1 out of every 2 women over age 50 develop a bone fracture in their lifetime due to osteoporosis. These fractures are most common at the hip, spine, and wrist and can result in serious morbidity and in some cases death. The incidence of osteoporosis in the U.S. is expected to increase significantly in the future as the population ages.

Prolia works to decrease the destruction of bone and increase bone mass and strength, and is recommended for administration subcutaneously once every 6 months.

In 2010, the FDA granted approval for Xgeva for the prevention of skeletal-related events (SREs) defined as any of the following: pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression, in individuals with bone metastases from solid tumors. In June 2013, the FDA approved additional indications for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity. Xgeva is not indicated for the prevention of SREs in individuals with multiple myeloma. In December 2014, the FDA granted an orphan designation and manufacturing approval for use in the United States for Xgeva in the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy (Product Information Label, 2016).

Bone metastases are associated with a risk of skeletal-related events (SREs), which include fracture, skeletal instability/loss of skeletal integrity requiring surgery or radiation, spinal cord compression, and hypercalcemia of malignancy.

In the United States there are 300-800 new cases of GCTB annually. The tumors are a benign but locally aggressive bone tumor that can spread in rare cases. Most germ cell tumors present as a large lytic mass which occurs most frequently in an end of a long tubular bone in young adults, often around joints. GCTB are slow growing and can result in swelling, impaired mobility and pathologic fractures when untreated. Surgery is the main treatment option for resectable GCTB; however, there is a relatively high tumor recurrence rate and an increased risk of tumor spread to other parts of the body. Xgeva provides a treatment option to adults and skeletally mature adolescents suffering from GCTB that cannot be adequately treated with surgery.

Hypercalcemia of malignancy is a complication of advanced cancer; in 2012 the United States prevalence was 2.7%. “HCM can result in renal failure, coma, and death, with an estimated 50% survival of 30 days regardless of treatment” (Hu, 2014).

Cummings and colleagues (2009) reported outcomes from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, a randomized, double-blind, placebo controlled trial. The participants were randomly assigned at the study site to receive subcutaneous (SQ) injections of either 60 mg of denosumab or placebo every 6 months for 36 months. The study enrolled 7869 postmenopausal women ages 60-90 who had bone mineral density (BMD) (T-score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip). Participants were randomly assigned to receive denosumab 60 mg SQ or placebo every 6 months for 36 months. Denosumab was found to reduce the cumulative incidence of new vertebral fractures by 68% in comparison to placebo (p<0.001). Incidence of hip and nonvertebral fractures was lower in the denosumab group, with relative risk reductions of 40% and 20%, respectively. The authors concluded:

Denosumab offers an alternative approach to the treatment of osteoporosis by decreasing bone resorption and increasing bone mineral density through the inhibition of RANKL. Denosumab was associated with a significant reduction in the risk of vertebral, hip, and nonvertebral fractures in postmenopausal women with osteoporosis.

In 2010, the American College of Rheumatology provided recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis, addressing counseling for lifestyle modifications and follow-up for individuals receiving glucocorticoids. Authors additionally state:

The smallest dose of glucocorticoid for the shortest duration possible was recommended as an important strategy to minimize osteoporosis risk. Since there may be no dose of glucocorticoids that does not accelerate bone loss or increase fracture risk, recommendations for counseling and assessment are extended to all doses of glucocorticoids used or expected to be used for at least 3 months.

In 2012, the Agency for Healthcare Research and Quality (AHRQ) published a Comparative Effectiveness Review on treatment to prevent fractures in men and women with low bone density or osteoporosis. The agency defines risk factors as follows:

Risk factors for osteoporotic fracture include (but are not limited to) increasing age, female, sex, postmenopause for women, hypogonadism or premature ovarian failure, low body weight, history of parental hip fracture, ethnic background (whites are at higher risk than blacks), previous clinical or morphometric vertebral fracture, previous fracture due to minimal trauma (i.e. previous osteoporotic fracture), rheumatoid arthritis, current smoking, alcohol intake (3 or more drinks/day), low BMD, vitamin D deficiency, low calcium intake, hyperkyphosis, falling, and immobilization, along with chronic use of certain medications, the most commonly implicated being glucocorticoids (GC), anticoagulants, anticonvulsants, aromatase inhibitors, cancer chemotherapeutic drugs, and gonadotropin-releasing hormone agonists.

Additionally, the review provided pharmacologic therapy recommendations for osteoporotic postmenopausal women and men; treatment includes bisphosphonate class of drugs, peptide hormones, estrogen for postmenopausal women, selective estrogen receptor modulators, and a monoclonal antibody. The reviewers conclude that:

The various agents used to prevent and treat osteoporosis have been linked with adverse effects, from the more common, mild effects (such as minor gastrointestinal complaints) to potentially serious issues. Some evidence suggests that these minor complaints, coupled with concerns about more serious effects, may affect the level of compliance with and persistence of treatment. Poor adherence and persistence may, in turn, affect the effectiveness of the treatments.

A single randomized, double-blind study compared denosumab with zoledronic acid (ZA) in the prevention of SREs for those with breast cancer and bone metastases (Stopeck, 2010). Participants were randomly assigned to receive either denosumab 120 mg subcutaneously (SQ) with intravenous (IV) placebo (n=1026) or ZA 4 mg IV adjusted for creatinine clearance with SQ placebo (n=1020). The trial primary endpoint was first on-study SRE defined as pathologic fracture, need for radiation or surgery to bone, or spinal cord compression. Endpoint results found denosumab to be superior over ZA in delaying time to first on-study SRE (hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.71 to 0.95; P=0.01 superiority). Authors concluded that:

Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

In a phase III randomized double-blind, placebo controlled study, denosumab was compared to ZA in the treatment of bone metastases in men with castration-resistant prostate cancer (Fizazi, 2011). There were 1901 participants eligible for efficacy analysis, 950 participants in the denosumab group and 951 in the ZA group. The absolute incidence of SREs was similar in the two groups, however, the reported median time to first on-study SRE was delayed by 3.6 months by denosumab compared to ZA (20.7 months vs. 17.1 months, p=0.0002 for non-inferiority, p=0.008 for superiority). Hypocalcaemia occurred in the denosumab group more often than in the ZA group (13% vs. 6%); osteonecrosis of the jaw (ONJ) occurred in 1-2% of participants, although many of the individuals who developed ONJ had preexisting dental problems.

The Non-Small Cell Lung Cancer (NSCLC) Clinical Practice Guideline™ of the National Comprehensive Cancer Network (NCCN®) recommends that denosumab can be considered in individuals with NSCLC and bone metastases. The recommendation is based on a 2A category of evidence (NCCN, 2017).

A phase III study evaluated by Scagliotti and colleagues (2012) compared the overall survival improvement in NSCLC with bone metastases in participants treated with monthly denosumab 120 mg SQ versus ZA 4 mg IV. Denosumab, when compared to ZA, was associated with median overall survival (9.5 vs. 8.0 months); HR=0.78; 95% CI, 0.65-0.94; p=0.01). In summary, “in this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.”

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guideline (2017) for Prostate Cancer states:

In men with castration-recurrent prostate cancer who have bone metastases, denosumab and zoledronic acid have been shown to prevent disease-related skeletal complications, which include fracture, spinal cord compression, or need for surgery or radiation therapy (RT) to bone. When compared to zoledronic acid, denosumab was shown to be superior in prevention of skeletal related events.

A phase III randomized, double-blind study reported by Henry and colleagues (2011) compared denosumab versus ZA in the delay or prevention of SREs for individuals with multiple myeloma or bone metastases (excluding breast or prostate cancer). There were 1776 participants enrolled in the study with bone metastases from a wide range of cancer types, including renal cell cancer (6%) not previously treated with a bisphosphonate. Study found denosumab non-inferior to ZA in delaying time to first on-study SRE (HR, 0.84; 95% CI, 0.71 to 0.98; p=0.0007). Authors concluded “denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a requirement for renal monitoring or dose adjustment.”

The National Comprehensive Cancer Network (NCCN), Clinical Practice Guidelines in Oncology for Thyroid Cancer states, intravenous bisphosphonate therapy or denosumab can be considered for the treatment of bone metastases, “data show that these agents prevent skeletal-related events.” The recommendation is based on a 2A category of evidence (NCCN, 2017).

Denosumab is being used as a treatment in GCTB. In 2012 Branstetter and colleagues published results from a phase II study of 20 participants who received 120 mg denosumab every 4 weeks after loading dose, with 20 of 20 participants reporting a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells. Authors concluded “denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone.”

In 2013, the FDA approval of Xgeva was based on demonstration of durable objective responses from two multicenter open label trials which enrolled adult and skeletally mature adolescents with histologically confirmed, measurable GCTB. Tumors were either recurrent, unresectable, or were located where planned surgery was likely to result in severe morbidity. Participants received Xgeva 120 mg SQ every 4 weeks with additional doses administered on day 8 and 15 of the first month of treatment. A total of 304 participants with a median age of 33 years (range 13-83 years, with a total of 10 skeletally mature adolescent’s ages 13-17 years) received Xgeva, of which 187 participants (61%) received radiographic assessment at baseline and at follow-up. A retrospective determination of objective response was performed by an independent review committee using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

According to the FDA:

An objective response was identified in 47 of 187 patients for an overall response rate of 25% (95% CI: 19, 32). All responses were partial responses. The estimated median time to response was 3 months. In the 47 patients with an objective response, the median duration of follow-up was 20 months (range: 2-44 months), and 51% (24/47) had responses lasting at least eight months. Three patients experienced disease progression following an objective response.

The safety data profile of Xgeva found that participants treated for GCTB were similar to that reported in bone metastases. Data was evaluated in 304 participants with GCTB who received at least 1 dose of Xgeva. Of these, 145 participants received treatment for at least 1 year. The most common adverse reactions reported were arthralgia, headache, nausea, back pain, fatigue, and pain in the extremity; while the most serious adverse reactions reported were found to be osteonecrosis of the jaw and osteomyelitis.

The National Comprehensive Cancer Network (NCCN), Clinical Practice Guidelines in Oncology for Bone Cancer includes denosumab as a single agent or combination therapy with radiation therapy or interferon alfa/peginterferon for treatment of localized disease and as a single agent in the treatment of metastatic GCTB. The recommendation is based on a 2A category of evidence (NCCN, 2017).

In 2014, the FDA approval of Xgeva for hypercalcemia of malignancy was based on primary analysis from an open-label, single-arm international study, which enrolled 33 participants with advanced cancer and persistent hypercalcemia after persistent IV bisphosphonate treatment (pamidronate 90 mg or zoledronic acid 4 mg) (Hu, 2014). The primary endpoint was:

The proportion of patients with response, pre-specified as CSC ≤ 11.5 mg/dL [2.9 mmol/L]; CT-CAE grade 0 or 1, corresponding to normal or mildly elevated calcium) within 10 days after the first dose of denosumab. CSC was calculated as: total serum calcium in milligrams per deciliter + [0.8 x (4 – serum albumin in grams per deciliter)] by day 19. Secondary endpoints included response by visit, duration or response, and the proportion of patients with a complete response (CRC ≤ 10.8 mg/dL [2.7 mmol/L)] by day 10 and during the study.

The study achieved its primary endpoint with a response rate at day 10 of 64 percent (n=21) in the 33 participants evaluated. The overall complete response rate was 64%. The estimated median time to response (CSC < 11.5 mg/dL) was 9 days, and the median duration of response was 104 days. The most common serious adverse reactions in participants receiving Xgeva for hypercalcemia of malignancy were worsening hypercalcemia (n=5, 15%) and dyspnea (n=3, 9%).

The FDA decision to exclude use of Xgeva in the prevention of SREs in individuals with multiple myeloma was based on analysis of a subgroup of participants with multiple myeloma comparing Xgeva to ZA. Mortality appeared to be higher for denosumab-treated participants compared to those in the control arm (hazard ratio [95% CI] of 2.26 [1.13, 4.50]; n=180). The limited number of participants in this subgroup precludes a definitive conclusion.

There are ongoing clinical trials evaluating the use of denosumab for other indications such as multiple myeloma and rheumatoid arthritis. However, at this time, there is a lack of evidence in the peer-reviewed medical literature in the form of phase III clinical trials to support the safety and efficacy for any other clinical indication.

Prolia:

Contraindications, Warnings and Precautions
The following are contraindications, warnings and precautions from the Product Information Label (2017):

Use in specific population:

Xgeva:

Contraindication, Warnings and Precautions
Xgeva is not recommended for use in the prevention of skeletal-related events in individuals with multiple myeloma (Product Information Label, 2016).

The following are contraindication, warnings and precautions from the Product Information Label (2016):

Use in specific population:

Definitions

Hypercalcemia: A condition characterized by abnormally high blood levels of calcium. It is defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL [3.0 mmol/L] using the formula: cCa in mg/dL=Ca in mg/dL + 0.8 (4.0 g/dL - patient albumin [g/dL]).

Metastatic: The spread of cancer from one part of the body to another; a metastatic tumor contains cells that are like those in the original (primary) tumor and have spread; also referred to as stage IV cancer.

Orphan Drug Designation: This special FDA designation was created in compliance with the Orphan Drug Act (ODA) which provides for granting special status to a product (drug) that treats a rare disease or condition upon request of a sponsor. The combination of the product to treat the rare disease or condition must meet certain criteria. This status is referred to as orphan designation.

Osteopenia: A condition of bone in which decreased calcification, decreased density, or reduced mass occurs (T-score of between -1.0 and -2.5 SD).

Osteoporosis: Loss of normal bone density, mass and strength, leading to increased porousness and vulnerability to fracture (defined as a T-score of -2.5 or less).

References

Peer Reviewed Publications:

  1. Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012; 18(16):4415-4424.
  2. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO clinical practice guidelines. Annals of Onc. 2014; 25(3):124-134.
  3. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361(8):756-765.
  4. Diel IJ, Body JJ, Stopeck AT, et al. The role of denosumab in the prevention of hypercalcemia of malignancy in cancer patients with metastatic bone disease. Eur J Cancer. 2015; 51(11):1467-1475.
  5. Ellis GK, Bone HG, Chlebowski R, et al. Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat. 2009; 118(1):81-87.
  6. Fizai 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.
  7. Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011; 29(9):1125-1132.
  8. Hu MI, Glezerman IG, Leboulleux S, et al, Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014; 99:3144-3152.
  9. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment. J Natl Cancer Inst. 2013; 105:1417-1420.
  10. Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res. 2012; 27(3):694-701.
  11. Rizzoli R, Body JJ, DeCensi A, et al. Guidance for the prevention of bone loss and factures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper. Osteoporos Int. 2012; 23:2567-2576.
  12. 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: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012; 7(12):1823-1829.
  13. Smith MR, Egerdie B, Toriz NH, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Eng J Med. 2009; 361(8):745-755.
  14. Stopeck AT, Lipton A, Body JJ, 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.
  15. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010; 11(3):275-280.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Agency for Healthcare Research and Quality. Treatment to prevent fractures in men and women with low bone density or osteoporosis: update of a 2007 Report. Comparative effectiveness review. 2012 March. Publication No 12-EHC023-EF. Available at: http://www.ncbi.nlm.nih.gov/books/NBK92566/pdf/TOC.pdf. Accessed on September 22, 2017.
  2. Amgen. Safety Study of Denosumab in subjects with recurrent or unresectable giant cell tumor of bone. NLM Identifier: NCT00680992. Last updated on June 5, 2017. Available at: https://clinicaltrials.gov/ct2/show/NCT00680992. Accessed on September 22, 2017.
  3. Amgen. Study of denosumab in the treatment of hypercalcemia of malignancy in subjects with elevated serum calcium. NLM Identifier: NCT00896454. Last updated on February 18, 2016. Available at: https://clinicaltrials.gov/ct2/show/NCT00896454. Accessed on September 22, 2017.
  4. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2015; 26(7):2045-2047.
  5. Denosumab Monograph. Lexicomp® Online, American Hospital Formulary Services ® (AHFS ®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised January 2, 2014. Accessed on September 22, 2017.
  6. Denosumab (systemic). In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated August 9, 2017. Available at: http://www.micromedexsolutions.com. Accessed on September 22, 2017.
  7. Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Revised 2017. Available at: https://www.rheumatology.org/Portals/0/Files/Guideline-for-the-Prevention-and-Treatment-of-GIOP.pdf. Accessed on September 22, 2017.
  8. NCCN Clinical Practice Guidelines in Oncology™ (NCCN). © 2017 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website at: http://www.nccn.org/index.asp. Accessed on September 22, 2017.
    • Bone Cancer (V.1.2018). Revised August 29, 2017.
    • Breast Cancer (V.2.2017) Revised April 6, 2017.
    • Kidney Cancer (V.1.2018). Revised September 7, 2017.
    • Non-Small Cell Lung Cancer (V.8.2017). Revised July 14, 2017.
    • Prostate Cancer (V.2.2017). Revised February 21, 2017.
    • Thyroid Carcinoma (V.2.2017). Revised May 17, 2017.
  9. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on September 27, 2017.
  10. National Institute of Health (NIH). Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement. 2000; 17(1):1-45. Available at: http://consensus.nih.gov/2000/2000Osteoporosis111html.htm. Accessed on September 22, 2017.
  11. National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. Revised June 12, 2014. Available at: https://my.nof.org/bone-soruce/education/clinicians-guide-to-the-prevention-and-treatment-of-osteoporosis. Accessed on September 22, 2017.
  12. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause. 2010; 17(1):25-54.
  13. Prolia [Product Information]. Thousand Oaks, CA. Amgen Inc.; May 26, 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125320s181lbl.pdf. Accessed on September 22, 2017.
  14. Van Poznak CH, Von Roenn JH, Temin S, et al. American Society of Clinical Oncology Clinical Practice Guideline Update on the Role of Bone-modifying agents in metastatic breast cancer. J Oncol Pract. 2011; 7(2):117-121.
  15. Watts NB, Bilezikian JP, Camacho PM, et al. American Association of Clinical Endocrinologists (AACE). American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010; 16 Suppl 3:1-37.
  16. Xgeva [Product Information]. Thousand Oaks, CA. Amgen Inc.; March 2, 2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125320Orig1s177lbl.pdf. Accessed on September 22, 2017.
Websites for Additional Information
  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis handout on health. February 2016. Available at: http://www.niams.nih.gov/Health_Info/Osteoporosis/default.asp. Accessed on September 22, 2017.
  2. National Institute of Health. Osteoporosis and Related Bone Diseases National Resource Center. Osteoporosis in men. June 2015. Available at: https://www.bones.nih.gov/health-info/bone/osteoporosis/men. Accessed on December 14, 2017.
  3. National Institute of Health. Osteoporosis and Related Bone Diseases National Resource Center. What is Osteoporosis? Updated November 2014. Available at: http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/osteoporosis_ff.asp. Accessed on September 22, 2017.
Index

Denosumab
Hypercalcemia of malignancy (HCM)
Prolia
Xgeva

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

New

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review.

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial document development. Moved content from DRUG.00055 Denosumab (Prolia®, Xgeva®) to new clinical utilization management guideline document with the same title.