Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Lanreotide (Somatuline® Depot)
Policy #:MA08.090b

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

MEDICALLY NECESSARY

Lanreotide (Somatuline® Depot) is considered medically necessary and, therefore, covered in individuals with any of the following indications when the corresponding criteria are met:

ACROMEGALY
  • For the long-term treatment of individuals with acromegaly who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.

NEUROENDOCRINE AND ADRENAL TUMORS
Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
  • For the treatment of unresectable, well- or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival.

Neuroendocrine Tumors of the Gastrointestinal Tract, Lung and Thymus (Carcinoid Tumors)
  • For the treatment of neuroendocrine tumors of the gastrointestinal tract, lung and thymus (carcinoid tumors) for any of the following indications:
    • Primary treatment for unresected primary gastrinoma
    • Management of distant metastatic bronchopulmonary/thymic disease if somatostatin receptor positive and/or
      • Experiencing hormonal symptoms, or if asymptomatic, low tumor burden and low grade (typical) histology
      • Chronic cough/dyspnea if multiple lung nodules or tumorlets and evidence of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)
    • Treatment of carcinoid syndrome
      • As a single agent
      • In combination with telotristat for persistent diarrhea due to poorly controlled carcinoid syndrome
      • In combination with other systemic therapy options for persistent symptoms such as flushing or diarrhea, or for disease progression
    • Management of locoregional advanced disease of the gastrointestinal tract and/or distant metastases*
      • Asymptomatic and a low tumor burden
      • Clinically significant tumor burden
      • For disease progression if not already receiving
    • Management of distant metastatic bronchopulmonary/ thymic disease* if somatostatin receptor positive and/or hormonal symptoms if clinically significant tumor burden and low grade (typical) histology, evidence of progression, or intermediate grade (atypical histology)
      • As primary therapy
      • As subsequent therapy if progression on first-line therapy
    • For management of locoregional unresectable bronchopulmonary/thymic disease* if somatostatin receptor positive and/or hormonal symptoms
      • As primary therapy in individuals with low grade (typical) histology
      • As subsequent therapy if progression on first-line therapy
    Neuroendocrine Tumors of the Pancreas

    For the treatment of neuroendocrine tumors of the pancreas for any of the following:
    • Tumor control** with locoregional advanced disease and/or distant metastatic disease; if disease progression, treatment with lanreotide should be continued for functional tumors in combination with any of the systemic therapy options: 
      • Treatment of asymptomatic, low tumor burden and stable disease
      • Treatment of symptomatic, clinically significant tumor burden, or clinically significant progression (if disease progression and not already receiving)
    • Management of symptoms related to hormone hypersecretion of locoregional disease for the therapy with lanreotide in combination with any of the following treatment options :
      • Treatment of gastrinoma (usually duodenal or head of pancreas)
      • Treatment of glucagonoma (usually tail)
      • Treatment of VIPoma
    Pheochromocytoma/Paraganglioma
    • For the treatment of locally unresectable disease or distant metastases if somatostatin receptor positive imaging and the individual is symptomatic.

    *If disease progression, treatment with lanreotide should be continued in individuals with functional tumors and may be used in combination with any of the systemic therapy options.

    ** For individuals with insulinoma, lanreotide should be used only if somatostatin scintigraphy is positive.

    EXPERIMENTAL/INVESTIGATIONAL

    All other uses for lanreotide (Somatuline® Depot) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

    REQUIRED DOCUMENTATION

    The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

    The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
    Policy Guidelines

    There is no Medicare coverage determination addressing lanreotide (Somatuline® Depot); therefore, the Company policy is applicable.

    Lanreotide (Somatuline® Depot) is administered via deep subcutaneous injection.

    BENEFIT APPLICATION

    Subject to the terms and conditions of the applicable Evidence of Coverage, lanreotide (Somatuline® Depot) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

    US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

    Lanreotide (Somatuline® Depot) was approved by the FDA on August 30, 2007 for the long-term treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy.

    Lanreotide (Somatuline® Depot) was approved by the FDA on December 16, 2014 for the treatment of individuals with unresectable, well- or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors to improve progression-free survival.

Description

    Somatostatin is a naturally occurring hormone that has many biological actions because its receptors are found throughout the entire body. Some actions of somatostatin include inhibiting the secretion of growth hormones (GH), prolactin, glucagon, and insulin. Because somatostatin has a short half-life and targets many different hormones, somatostatin analogs were created (e.g., lanreotide [Somatuline® Depot]). Somatostatin analogs have a long half-life so they can be dosed less often, as well as greater inhibitory selectivity of GH secretion over insulin secretion.

    Lanreotide (Somatuline® Depot) is indicated for the long-term treatment of acromegaly, a rare condition characterized by abnormal enlargement of bones in the extremities and head, as well as thickening of soft tissues, such as the heart, lips, and tongue. Acromegaly occurs when the pituitary gland produces too much GH, which in turn causes excess secretion of insulin-like growth factor-1 (IGF-1). Lanreotide (Somatuline® Depot) suppresses the secretion of GH and insulin-like growth factor 1 (IGF-1) in individuals who have had inadequate response to or cannot be treated with other therapies, including surgery or radiotherapy, by binding to somatostatin receptors.

    Lanreotide (Somatuline® Depot) is also indicated for the treatment of unresectable, well- or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors. Data have shown that lanreotide (Somatuline® Depot) exhibits antiproliferative effects on these tumors, and improves progression-free survival. Neuroendocrine tumors are a heterogeneous group of neoplasms that arise from neuroendocrine cells and their precursors located throughout the body. Individuals with metastases from neuroendocrine tumors often become symptomatic due to hormone hypersecretion rather than tumor bulk. Lanreotide (Somatuline® Depot) is highly effective in controlling the symptoms associated with neuroendocrine tumors, such as flushing and diarrhea.

    CLINICAL STUDIES

    ACROMEGALY
    The efficacy of lanreotide (Somatuline® Depot) on reducing growth hormone and insulin-like growth factor 1 was evaluated in two trials. The first was a three-phase trial which included a four-week, double-blind, placebo-controlled phase; a 16-week, single-blind, fixed-dose phase; and a 32-week, open-label dose titration phase. A total of 107 individualss completed the placebo-controlled phase, 105 completed the fixed-dose phase, and 99 completed the dose-titration phase. In the first (double-blind) phase of the trial, 52 of 83 (63 percent) of the lanreotide (Somatuline® Depot)--treated individuals had greater than 50 percent decrease in mean GH from baseline to week four, compared to 0 in the placebo group. In the fixed-dose phase, 72 percent of the 107 lanreotide (Somatuline® Depot)--treated individuals had a decrease from baseline in mean GH of greater than 50 percent. This efficacy was maintained for the duration of the trial.

    The second trial was a 48-week, open-label, uncontrolled, multicenter study that enrolled individuals with an IGF-1 level equal to or greater than 1.3 times the upper limit of normal. This trial began with a four-month fixed-dose phase where individuals received four deep subcutaneous injections of lanreotide (Somatuline® Depot) at four-week intervals. This was followed by a dose-titration phase where the dose of lanreotide (Somatuline® Depot) was adjusted based on GH and IGF-1 levels. Sixty-three individuals started the fixed-dose phase and 57 completed 48 weeks of treatment. At the completion (48 weeks) of the trial, 43 percent (27/63) achieved normal age-adjusted IGF-1 levels, 38 percent (24/63) individuals achieved both normal IGF-1 levels and GH levels less than or equal to 2.5ng/mL, and 27 percent (17/63) had both normal IGF-1 levels and GH levels less than 1ng/mL.

    GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS
    Efficacy of lanreotide (Somatuline® Depot) in the treatment of gastroenteropancreatic neuroendocrine tumors was evaluated in a multicenter, randomized, double-blind, placebo-controlled trial of 204 individuals. Individuals received either lanreotide (Somatuline® Depot) or placebo every 4 weeks until disease progression, unacceptable toxicity, or a maximum of 96 weeks. Primary outcome was progression-free survival. Individuals in the lanreotide (Somatuline® Depot) arm had statistically significant improvement in progression-free survival compared to those in the placebo arm. Median progression-free survival was not reached in the lanreotide (Somatuline® Depot) group, and was 16.6 months in the placebo group.

    OFF-LABEL INDICATION

    There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
    References

    American Hospital Formulary Service (AHFS). Drug Information 2019. Lanreotide. [Lexicomp Online Web site]. 02/22/19. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 26, 2019.

    Colao A, Faggiano A, Pivonello R. Somatostatin analogues: treatment of pituitary and neuroendocrine tumors. In: L. Martini, eds. Prog Brain Res. 2010;182:281-94.

    Elsevier’s Gold Standard Clinical Pharmacology Compendium.Lanreotide. 02/28/2018. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed November 26, 2019.

    Fleseriu M. Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review. Pituitary. 2011;14(2):184-93.

    Lexi-Drugs Compendium. Lanreotide. 12/21/19. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed November 26, 2019.

    Ludlam WH, Anthony L. Safety review: dose optimization of somatostatin analogs in patients with acromegaly and neuroendocrine tumors. Adv Ther. 2011;28(10):825-41. Epub 2011 Sep 28.

    Melmed S, Savarese D, Treatment of acromegaly. 08/20/2019. [Uptodate Web site] Available at: http://www.uptodate.com/contents/treatment-of-acromegaly [via subscription only]. Accessed November 26, 2019.

    National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Neuroendocrine and AdrenalTumors. V1.2019. 03/05/19. [NCCN Web site]. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site [via free subscription]. Accessed November 26, 2019.

    National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium.Lanreotide. [NCCN Web site]. 2019. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=382 [via subscription only]. Accessed November 26, 2019.

    Strosberg JR. Treatment of the carcinoid syndrome. 07/09/2019. Available at: https://www.uptodate.com/contents/treatment-of-the-carcinoid-syndrome?source=search_result&search=treatment%20of%20carcinoid%20syndrome&selectedTitle=1~78 [via subscription only]. Accessed November 26, 2019.

    Micromedex® Healthcare Series [Internet database]. Lanreotide. 11/06/2019. Greenwood Village, C: ThomsonMicromedex® . Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 26, 2019.

    US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Lanreotide (Somatuline® Depot) drug label [FDA Web site]. updated 04/2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022074s010lbl.pdf. Accessed November 26, 2019.

    US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Lanreotide (Somatuline® Depot) drug label and approval letter [FDA Web site]. updated 02/04/2019. Available at:
    http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2007/022074s000ltr.pdf. Accessed November 26, 2019.


    Coding

    Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

    The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

    In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

    The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A


HCPCS Level II Code Number(s)

J1930 Injection, lanreotide, 1 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Lanreotide (Somatuline® Depot)





Policy History

    MA08.090b
    12/30/2019.This version of the policy will become effective 12/30/2019.

    This policy was updated to communicate the coverage position changes for neuroendocrine and adrenal tumors (pheochromocytoma/paraganglioma, neuroendocrine tumors of the gastrointestinal tract, lung and thymus [carcinoid tumors], neuroendocrine tumors of the pancreas) in accordance with the National Comprehensive Cancer Network (NCCN).

    MA08.090a
    11/19/2018This version of the policy will become effective 11/19/2018.

    This policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN) compendium. Included criteria for neuroendocrine tumors


    MA08.090
    01/01/2018This version of the policy will become effective 01/01/2018.

    This new policy has been developed to communicate the Company’s coverage criteria for lanreotide (Somatuline® Depot).





    Version Effective Date: 12/30/2019
    Version Issued Date: 12/30/2019
    Version Reissued Date: N/A