Original Issue Date (Created): 11/1/2010 Most Recent Review Date (Revised): 1/18/2018 Effective Date: 9/1/2018 POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY I. POLICY Denosumab (Prolia ) Denosumab (Prolia ) may be considered medically necessary for the treatment of osteoporosis in postmenopausal women and men when the patient is receiving supplemental calcium and vitamin D and any ONE of the following indications are met: History of a hip or vertebral (clinical or morphometric) fracture, fragility or low-impact fracture, or multiple risks of fracture (see policy guidelines); or Bone mineral density (BMD) T score of [-2.5] or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes; or The patient has contraindications or is unresponsive to oral osteoporosis agents. Denosumab (Prolia ) may be considered medically necessary for the following cancerrelated indications: To increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer; or To increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. Denosumab (Prolia ) for all other indications than those listed above is considered investigational. There is insufficient evidence to support a conclusion concerning the health outcomes or benefits associated with this drug. Page 1
Denosumab (Xgeva ) Denosumab (Xgeva ) may be considered medically necessary for the following: Prevention of skeletal-related events in patients with multiple myeloma and 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 Denosumab (Xgeva ) for all other indications than those listed is considered investigational. There is insufficient evidence to support a conclusion concerning the health outcomes or benefits associated with this drug. Policy Guidelines Patients receiving Prolia should not receive Xgeva - same active ingredient. All postmenopausal women and men age 50 and older should be evaluated for osteoporosis risk in order to determine the need for BMD testing and/or vertebral imaging. In general, the more risk factors that are present, the greater the risk of fracture. The FRAX tool has been developed by WHO to evaluate fracture risk of patients. It is based on individual patient models that integrate the risks associated with clinical risk factors as well as bone mineral density (BMD) at the femoral neck. Use of WHO Fracture Risk Algorithm (FRAX ) in the U.S. FRAX was developed to calculate the 10-year probability of a hip fracture and the 10- year probability of a major osteoporotic fracture (defined as clinical vertebral, hip, forearm or proximal humerus fracture) taking into account femoral neck BMD and the clinical risk factors shown in the table below. The FRAX algorithm is available at www.nof.org and at www.shef.ac.uk/frax. It is also available on newer DXA machines or with software upgrades that provide the FRAX scores on the bone density report. Page 2
FRAX is most useful in patients with low femoral neck BMD. Utilizing FRAX in patients with low BMD at the lumbar spine but a relatively normal BMD at the femoral neck underestimates fracture risk in these individuals. Specifically, the WHO algorithm has not been validated for the use of lumbar spine BMD. NOF recommends treatment of individuals with osteoporosis of the lumbar spine as well as the hip. Application of U.S.-FRAX in the U.S FRAX is intended for postmenopausal women and men age 50 and older; it is not intended for use in younger adults or children, however the FRAX tool has been validated for use in men and women from age 40 to 90. The FRAX tool has not been validated in patients currently or previously treated with pharmacotherapy for osteoporosis. In such patients, clinical judgment must be exercised in interpreting FRAX scores. The following examples of untreated patients are offered21: a) No ET/HT or estrogen agonist/antagonist (SERM) for the past one year b) No calcitonin for the past one year c) No PTH for the past one year d) No denosumab for the past one year e) No bisphosphonate for the past two years (unless it is an oral taken for <2 months) Note: Calcium and vitamin D do NOT constitute treatment in this context. FRAX can be calculated with either femoral neck BMD or total hip BMD but when available, femoral neck BMD is preferred. The use of BMD from non-hip sites is not recommended. The WHO determined that for many causes of secondary osteoporosis, fracture risk was mediated primarily through impact on BMD. For this reason, when femoral neck BMD is inserted into FRAX, the secondary osteoporosis button is automatically inactivated Conditions, Diseases and Medications That Cause or Contribute to Osteoporosis and Fractures Lifestyle factors Alcohol Abuse High salt intake Falling Low calcium intake Inadequate physical activity Excessive thinness Vitamin D insufficiency Immobilization Excess Smoking (active or passive) Page 3
Genetic factors Cystic fibrosis Homocystinuria Osteogenesis imperfect Ehlers-Danlos Hypophosphatasia Parental history of hip fracture Gaucher s disease Idiopathic hypercalciuria Porphyria Glycogen storage diseases Marfan syndrome Riley-Day syndrome Hemochromatosis Hypogonadal states Menkes steely hair syndrome Androgen insensitivity Hyperprolactinemia Premature ovarian failure Anorexia nervosa and bulimia Premature menopause Athletic amenorrhea Turner s & Klinefelter s syndromes Panhypopituitarism Endocrine disorders Adrenal insufficiency Cushing s syndrome Central Adiposity Diabetes mellitus (Types 1 & 2) Hyperparathyroidism Thyrotoxicosis Gastrointestinal disorders Celiac disease Inflammatory bowel disease Primary biliary cirrhosis Gastric bypass GI surgery Hematologic disorders Malabsorption Pancreatic disease Multiple myeloma Monoclonal gammopathies Sickle cell disease Hemophilia Leukemia and lymphomas Systemic mastocytosis Thalassemia Rheumatologic and autoimmune diseases Ankylosing spondylitis Lupus Rheumatoid arthritis Other rheumatic and autoimmune diseases Central nervous system disorders Epilepsy Parkinson s disease Stroke Multiple sclerosis Spinal cord injury Miscellaneous conditions and diseases AIDS/HIV Congestive heart failure Muscular dystrophy Page 4
Alcoholism Depression Post-transplant bone disease Amyloidosis End stage renal disease Sarcoidosis Chronic metabolic acidosis Hypercalciuria Weight loss Chronic obstructive lung disease Idiopathic scoliosis Medications Aluminum (in antacids) Cyclosporine A and tacrolimus Proton pump inhibitors Anticoagulants (heparin) Depo-medroxyprogesterone Selective serotonin reuptake (premenopausal inhibitors contraception) Anticonvulsants Aromatase inhibitors Barbiturates Glucocorticoids ( 5 mg/d prednisone or equivalent for 3 months) GnRH (Gonadotropin releasing hormone) antagonists and agonists Lithium Cancer chemotherapeutic Methotrexate drugs From: The Surgeon General s Report, with modification Cross-references: Tamoxifen (premenopausal use) Thiazolidinediones (such as Actos and Avandia ) Thyroid hormones (in excess) Parenteral nutrition MP-2.103 Off-Label Use of Medications MP-2.220 Bone Turnover Markers For Diagnosis and Management of Osteoporosis and Diseases Associated with High Bone Turnover MP-2.143 Zoledronic Acid (Reclast, Zometa ) MP-5.037 Whole Body Dual X-ray Absorptiometry to Determine Body Composition II. PRODUCT VARIATIONS TOP This policy is only applicable to Medicare Advantage products administered by Capital BlueCross. For all other products, please refer to Prime Therapeutics policy for any preauthorization and medical necessity requirements related to drugs covered under a member s medical benefit. Page 5
Notes: 1. FDA approved drugs used for indications other than what is indicated on the FDA approved product label may be covered under Medicare if it is determined that the use is medically accepted, taking into consideration the Medicare recognized national drug compendia, authoritative medical literature and/or accepted standards of medical practice. Refer to Medicare Benefit Policy Manual (100-2, Chapter 15, Section 50.4.2- Unlabeled Use of Drug). http://www.cms.gov/manuals/downloads/bp102c15.pdf 2. In accordance with CMS letter issued on September 17, 2012, entitled Prohibition on Imposing Mandatory Step Therapy for Access to Part B Drugs and Services. Step therapy that is not part of the FDA label does not apply to Medicare Advantage. III. DESCRIPTION/BACKGROUND Denosumab (Prolia ) TOP Osteoporosis is a condition characterized by a loss of bone mass that occurs throughout the skeleton, which predisposes a patient to fractures. The Dual energy X-ray absorptiopmetry (DEXA) measures bone mineral density with results reported as a T- score. T-scores are reported according to standard deviations (SD) of World Health Criteria. The BMD diagnosis of normal, low bone mass, osteoporosis and severe or established osteoporosis is based on the WHO diagnostic classification: Normal: - T-score within 1 SD of a young normal adult Osteopenia-T-score of -1 to 2.5 SD below that of a young normal adult Osteoporosis- T-score of -2.5 or less SD below that of a young normal adult Severe osteoporosis- T-score of -2.5 or less SD below normal with fragility fractures Denosumab (Prolia, Amgen) is the first monoclonal antibody approved in the U.S. for the treatment of postmenopausal osteoporosis.. The drug was approved by the U.S. Food and Drug Administration (FDA) on June 1, 2010 It inhibits osteoclast-mediated bone resorption; thus, it is an antiresorptive agent like the bisphosphonates but has a different mechanism of action. Denosumab is a fully human monoclonal antibody which specifically targets the receptor activity of nuclear factor kappa B ligand (RANKL). RANKL is a protein which is essential for the formation, survival and function of osteoclasts, which are the cells responsible for bone resorption. On September 19, 2011, the U.S. Food and Drug Administration (FDA) approved two new indications for Prolia (denosumab) as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and Page 6
as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer. On September. 20, 2012 the U.S. Food and Drug Administration (FDA) approved Prolia (denosumab) as a treatment to increase bone mass in men with osteoporosis at high risk for fracture. Prolia, the first FDA-approved RANK Ligand inhibitor, is a subcutaneous injection administered by a health care professional every six months. While osteoporosis and osteoporosis-related fractures are more commonly associated with postmenopausal women, osteoporosis in men is a significant issue that is increasing in prevalence as life expectancies rise, According to the National Osteoporosis Foundation, two million men in the U.S. have osteoporosis and another 12 million are at risk. Osteoporosis and osteoporotic fractures in men remain under diagnosed and under treated. Denosumab (Xgeva ) Xgeva is a monoclonal antibody that targets a protein involved in cancer-related bone destruction called human RANKL. Other FDA-approved drugs for similar conditions include Zometa (zoledronic acid) and Aredia (pamidronate disodium). Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia. Xgeva is available as a 120mg/1.7mL single-use vial. Skeletal-related events (SRE s) On November 19, 2010, the U.S. Food and Drug Administration (FDA) approved Amgen s (Xgeva ) (denosumab) for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Skeletal-related events include bone fractures from cancer and bone pain requiring radiation. For patients with bone metastasis from solid tumors, XGEVA is administered as a subcutaneous injection (120 mg) every four weeks in the upper arm, upper thigh, or abdomen. On January 5, 2018, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sbla) for XGEVA (denosumab) to expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. The approval is based on data from the pivotal Phase 3 '482 study, the largest international multiple myeloma clinical trial ever conducted, which enrolled 1,718 patients. Page 7
Hypercalcemia of malignancy On Dec. 8, 2014 the U.S. Food and Drug Administration (FDA) approved Xgeva (denosumab) for the treatment of hypercalcemia of malignancy (HCM) refractory to bisphosphonate therapy. Xgeva was approved and granted Orphan Drug Designation by the FDA, which is reserved for drugs that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the U.S. HCM is a serious complication in patients with advanced cancer, including those with hematologic malignancies, and indicates poor prognosis. 1, 2 The condition results from cancer-driven increases in bone resorption, and if untreated, can lead to renal failure, progressive mental impairment, coma and death. For patients with hypercalcemia of malignancy, XGEVA is administered as a subcutaneous injection (120 mg) every four weeks with additional 120 mg doses on days eight and 15 of the first month of therapy Giant cell tumor of bone On June 13, 2013 the U.S. Food and Drug Administration (FDA) approved XGEVA (denosumab) for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone (GCTB) that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA was approved following a priority review by the FDA, a designation reserved for drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. GCTB typically affects individuals between the ages of 20 to 40. The disease is characterized by a bone destructive tumor that often results in fractures. When untreated, it often results in complete destruction of the affected bone, leading to bone fracture, joint dysfunction, deformity or amputation. For patients with GCTB, XGEVA is administered as a subcutaneous injection (120 mg) every four weeks with additional 120 mg doses on days eight and 15 of the first month of therapy. IV. RATIONALE TOP For information on clinical studies for denosumab (Prolia and Xgeva), refer to the Prescribing Information. Page 8
V. DEFINITIONS TOP BONE RESORPTION is bone loss due to osteoclastic activity. FRACTURE is a traumatic injury to a bone in which the continuity of the bone tissue is broken. MENOPAUSE cessation of menses as a result of failure of follicular maturation in the presence of elevated gonadotropin. OSTEOCLASTIC refers to osteoclasts, especially with reference to their activity in the absorption and removal of osseous (bone) tissue. OSTEOCLASTS are large multinucleated cells formed from differentiated macrophages that are responsible for the breakdown of bone. VI. BENEFIT VARIATIONS TOP The existence of this medical policy does not mean that this service is a covered benefit under the member's contract. Benefit determinations should be based in all cases on the applicable contract language. Medical policies do not constitute a description of benefits. A member s individual or group customer benefits govern which services are covered, which are excluded, and which are subject to benefit limits and which require preauthorization. Members and providers should consult the member s benefit information or contact Capital BlueCross for benefit information. VII. DISCLAIMER TOP Capital BlueCross s medical policies are developed to assist in administering a member s benefits, do not constitute medical advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of members. Members should discuss any medical policy related to their coverage or condition with their provider and consult their benefit information to determine if the service is covered. If there is a discrepancy between this medical policy and a member s benefit information, the benefit information will govern. Capital BlueCross considers the information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law. VIII. CODING INFORMATION TOP Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as Page 9
coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement. Covered when medically necessary: HCPCS Code Description J0897 Injection, denosumab, 1 mg (i.e., Prolia, Xgeva ) The following diagnoses are considered medically necessary for Prolia. All other indications are considered investigational, and therefore will not be covered. ICD-10-CM Diagnosis Description Codes C50.011 Malignant neoplasm of nipple and areola, right female breast C50.012 Malignant neoplasm of nipple and areola, left female breast C50.019 Malignant neoplasm of nipple and areola, unspecified female breast C50.111 Malignant neoplasm of central portion of right female breast C50.112 Malignant neoplasm of central portion of left female breast C50.119 Malignant neoplasm of central portion of unspecified female breast C50.211 Malignant neoplasm of upper-inner quadrant of right female breast C50.212 Malignant neoplasm of upper-inner quadrant of left female breast C50.219 Malignant neoplasm of upper-inner quadrant of unspecified female breast C50.311 Malignant neoplasm of lower-inner quadrant of right female breast C50.312 Malignant neoplasm of lower-inner quadrant of left female breast C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast C50.411 Malignant neoplasm of upper-outer quadrant of right female breast C50.412 Malignant neoplasm of upper-outer quadrant of left female breast C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast C50.511 Malignant neoplasm of lower-outer quadrant of right female breast C50.512 Malignant neoplasm of lower-outer quadrant of left female breast Page 10
ICD-10-CM Diagnosis Codes Description C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast C50.611 Malignant neoplasm of axillary tail of right female breast C50.612 Malignant neoplasm of axillary tail of left female breast C50.619 Malignant neoplasm of axillary tail of unspecified female breast C50.811 Malignant neoplasm of overlapping sites of right female breast C50.812 Malignant neoplasm of overlapping sites of left female breast C50.819 Malignant neoplasm of overlapping sites of unspecified female breast C50.911 Malignant neoplasm of unspecified site of right female breast C50.912 Malignant neoplasm of unspecified site of left female breast C50.919 Malignant neoplasm of unspecified site of unspecified female breast C61 Malignant neoplasm of prostate C79.81 Secondary malignant neoplasm of breast D29.1 Benign neoplasm of prostate D49.3 Neoplasm of unspecified behavior of breast M80.00XA M80.00XD M80.00XG M80.00XK M80.00XP M80.00XS Age-related osteoporosis with current pathological fracture, unspecified site, initial encounter for fracture Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with routine healing Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with delayed healing Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with nonunion Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with malunion Age-related osteoporosis with current pathological fracture, unspecified site, sequela Page 11
ICD-10-CM Diagnosis Codes M80.08XA M80.08XD M80.08XG M80.08XK M80.08XP M80.08XS M80.80XA M80.80XD M80.80XG M80.80XK M80.80XP M80.80XS M80.88XA M80.88XD M80.88XG Description Age-related osteoporosis with current pathological fracture, vertebra(e), initial encounter for fracture Age-related osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with routine healing Age-related osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with delayed healing Age-related osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with nonunion Age-related osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with malunion Age-related osteoporosis with current pathological fracture, vertebra(e), sequela Other osteoporosis with current pathological fracture, unspecified site, initial encounter for fracture Other osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with routine healing Other osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with delayed healing Other osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with nonunion Other osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with malunion Other osteoporosis with current pathological fracture, unspecified site, sequela Other osteoporosis with current pathological fracture, vertebra(e), initial encounter for fracture Other osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with routine healing Other osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with delayed healing Page 12
ICD-10-CM Diagnosis Codes M80.88XK M80.88XP M80.88XS Description Other osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with nonunion Other osteoporosis with current pathological fracture, vertebra(e), subsequent encounter for fracture with nonunion Other osteoporosis with current pathological fracture, vertebra(e), sequela M81.0 Age-related osteoporosis without current pathological fracture M81.6 Localized osteoporosis [Lequesne] M81.8 Other osteoporosis without current pathological fracture M85.80 Other specified disorders of bone density and structure, unspecified site M85.88 Other specified disorders of bone density and structure, other site M85.89 Other specified disorders of bone density and structure, multiple sites M85.9 "Disorder of bone density and structure, unspecified Z85.3 Personal history of malignant neoplasm of breast Z87.310 Personal history of (healed) osteoporosis fracture Z87.311 Personal history of (healed) other pathological fracture Z87.312 Personal history of (healed) stress fracture Z79.811 Long term (current) use of aromatase inhibitors Z79.818 Long term (current) use of other agents affecting estrogen receptors and estrogen levels The following diagnoses are considered medically necessary for Xgeva. All other indications are considered investigational, and therefore will not be covered. ICD-10-CM Diagnosis Codes Description C79.51 Secondary malignant neoplasm of bone C90.00 Multiple myeloma not having achieved remission Page 13
ICD-10-CM Diagnosis Description Codes C90.01 Multiple myeloma in remission C90.02 Multiple myeloma in relapse D48.0 Neoplasm of uncertain behavior of bone and articular cartilage E83.52 Hypercalcemia IX. REFERENCES TOP Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual. Publication 100-02. Chapter 15. Section 50.4.2. Unlabeled Use of Drug. Effective 10/01/03. [Website]: http://www.cms.gov/manuals/downloads/bp102c15.pdf Accessed January 18, 2018. Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual. Publication 100-02. Chapter 15. Section 50.4.5. Off-Label Use of Anti- Cancer Drugs and Biologicals. [Website]: http://www.cms.gov/manuals/downloads/bp102c15.pdf Accessed January 18, 2018. Centers for Medicare and Medicaid Services (CMS) Medicare Benefit Policy Manual Publication 100-02. Chapter 15 Sections 50, 50.4.1, 50.4.3 Drugs and Biologicals Effective 10/01/03. [Website]: http://www.cms.gov Accessed January 18, 2018. Taber s Cyclopedic Medical Dictionary 20th edition Denosumab (Prolia ) BCBSA Specialty Pharmacy Combined Capacity (SPCC) Report #8-2010. Denosumab (Prolia ) December 2010. Cummings SR, San Martin J, et al. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engle J Med 361; 8 August 20, 2009. FRAX WHO Fracture Risk Assessment Tool [Website]: http://www.shef.ac.uk/frax/tool.jsp. Accessed January 18, 2017. Lerwicki, M. Ostéoporotic Fracture Risk Assessment In: UpToDate Online Journal [serial online]. Waltham, MA: UpToDate; updated January 4, 2018. [Website]: www.uptodate.com. Accessed January 18, 2018. Page 14
National Institute for Health and Clinical Excellence (NICE). Denosumab for the prevention of osteoporotic fractures in postmenopausal women. Clinical Guidance TA204. October 2010. [Website]: https://www.nice.org.uk/guidance/ta204 Accessed January 18, 2018. Prolia (denosumab) prescribing information. Revised 01/17.Prolia [Website]: http://pi.amgen.com/united_states/prolia/prolia_pi.pdf Accessed January 18, 2018. WHO Fracture risk assessment tool. [Website]: http://www.iofbonehealth.org/health-professionals/aboutosteoporosis/diagnosis.html Accessed January 18, 2018. Denosumab (Xgeva ) BCBSA Specialty Pharmacy Combined Capacity (SPCC) Report #8/15 Denosumab (Prolia.Xgeva ) December 2010. Smith MR, Egerdie B, et al. Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer N Engl J Med 361; 8 August 20, 2009 The National Osteoporosis Foundation [Website]: http://www.nof.org/ Accessed January 18, 2018. PR Newswire. January 5, 2018. FDA Approves XGEVA (denosumab) For The Prevention Of Skeletal-Related Events In Patients With Multiple Myeloma. [Website]: https://finance.yahoo.com/news/fda-approves-xgeva-denosumabprevention-140000611.html Accessed January 18, 2018. Xgeva (denosumab) prescribing information. Revised 01/18..Xgeva [Website]: http://pi.amgen.com/~/media/amgen/repositorysites/pi-amgencom/xgeva/xgeva_pi.pdf Accessed January 18, 2018. X. POLICY HISTORY TOP CAC 9/27/10 New Policy. CAC 10/25/11 Consensus review. CAC 11/22/11 Minor revision to add recent (9/19/2011 ) FDA approved cancer-related indications for treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer. These indications will not require preauthorization. CAC 10/30/12 Consensus review. References updated but no changes to the policy statements. Medicare variation revised to state step therapy Page 15
does not apply. Codes reviewed 10/25/12 CAC 7/30/13 Minor. Denosumab (Prolia ) and Denosumab (Xgeva ) combined into one policy. MP 2.157 Denosumab (Xgeva ) retired. Indications for treatment of men with osteoporosis added as a medically necessary indication for Prolia. 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 added as an indication for Xgeva. Admin code review. CAC 3/25/14 Consensus review. References updated. No changes to the policy statements. Rationale added. Medicare variation revised. Admin code review. Added 198.5. Admin change 7/1/14 deleted notation regarding preauthorization requirement. All Users should refer to officially posted preauthorization resources for requirements. CAC 3/24/15 Minor. Added hypercalcemia of malignancy as a medically necessary indication for Xgeva. Other policy statements unchanged. References and rationale updated. CAC 1/26/16 Coding review. No changes to the policy statements. References updated. FEP variation revised to refer to the FEP medical policy manual. Coding updated. Admin update 1/1/17: Product variation section reformatted CAC 3/28/17 Consensus review. No changes to the policy statements. References updated. Coding reviewed. Coding updated 4/20/17 Admin update 9/1/17: Administrative wording corrections to policy statement. Admin update 6/1/18: Effective 6/1/18 for Medicare Advantage only. See Prime Therapeutics for all other products. 1/18/18 Minor revision. Policy revised to add the new FDA-approved indication for the prevention of skeletal-related events in patients with multiple myeloma. Previously, this indication had been considered investigational. Background and references updated. Rationale section revised to refer to the prescribing information for the clinical studies. Coding reviewed. Effective 9/1/18. Top Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance Company, Capital Advantage Assurance Company and Keystone Health Plan Central. Independent licensees of the BlueCross BlueShield Association. Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies. Page 16