Commercial

Medical Policy

Notification

Lanreotide (Somatuline® Depot)

Notification Issue Date:

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).

Title:

Lanreotide (Somatuline® Depot)

Policy #:

08.01.40h

Policy

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.

MEDICALLY NECESSARY

Lanreotide (Somatuline® Depot) is considered medically necessary and, therefore, covered in individuals with the following conditions 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 (Well-Differentiated Grade 1/2), Lung and Thymus (Carcinoid Tumors)

For symptom and/or tumor control of recurrent, locoregional advanced disease and/or distant metastases* of the gastrointestinal tract

As a single agent if surgical cytoreduction of metastases not possible and low tumor burden
As a single agent for disease progression (if not already receiving) following resection of primary, regional lymph nodes and metastases
As a single agent for disease progression (if not already receiving) following resection of primary tumor if symptomatic and/or following observation if surgical cytoreduction of metastases not possible and low tumor burden
As a single agent or in combination with alternative front-line therapy if surgical cytoreduction of metastases not possible and clinically significant tumor burden (National Comprehensive Cancer Network [NCCN] preferred)
As subsequent therapy a single agent or in combination with subsequent therapy options for clinically significant disease progression (NCCN preferred)
At above label dosing after clinical, symptomatic, or radiographic progression (if somatostatin receptor [SSTR]-positive) on standard doses

For symptom and/or tumor control of recurrent and/or locoregional unresectable lung/thymic disease* if somatostatin receptor positive and/or hormonal symptoms

As first-line therapy
As subsequent therapy (as alternate first-line therapy) if progression on first-line therapy

For symptom and/or tumor control of recurrent and/or distant metastatic lung/thymic disease* if somatostatin receptor positive and/or hormonal symptoms

As first-line therapy (preferred if clinically significant tumor burden and low grade [typical carcinoid], evidence of disease progression, intermediate grade [atypical carcinoid], or symptomatic)
As subsequent therapy (as alternate first-line therapy) if progression on first-line therapy if clinically significant tumor burden and low grade (typical carcinoid), evidence of disease progression, intermediate grade (atypical carcinoid), or symptomatic (NCCN preferred)

For symptom control of multiple lung nodules or tumorlets and evidence of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) as first-line therapy if chronic cough/dyspnea is not responsive to inhalers or conventional treatment
For symptom control of carcinoid syndrome
- As a single agent
- In combination with telotristat for diarrhea due to poorly controlled carcinoid syndrome
- In combination with other systemic therapy options (based on disease site) with or without telotristat for persistent symptoms (i.e., flushing, diarrhea) due to poorly controlled carcinoid syndrome

Treatment of carcinoid syndrome for any of the following regimens:

As a single agent
In combination with telotristat for persistent diarrhea due to poorly controlled carcinoid syndrome
In combination with other systemic therapy options (based on disease site) with or without telotristat for persistent symptoms (i.e., flushing, diarrhea) due to poorly controlled carcinoid syndrome

Neuroendocrine and Adrenal Tumors - Well-Differentiated Grade 3 Neuroendocrine Tumors

For the treatment and/or tumor control of SSTR-positive (if SSTR-positive and/or hormonal symptoms) for unresectable locally advanced/metastatic disease with favorable biology (e.g., relatively low Ki-67 [<55%], slow growing, positive SSR-based PET imaging) at standard dose

Pheochromocytoma/Paraganglioma

Treatment for secreting tumors for hormone excess and symptom control of locally unresectable disease or distant metastases (if SSTR-positive)

Tumors of the Pancreas (Well-Differentiated Grade 1/2)

Management of symptoms and/or tumor control of locoregional disease with any of the following indications:

Gastrinoma (usually duodenal or head of the pancreas)
Insulinoma only if tumor expresses somatostatin receptors
Glucagonoma (usually tail)
VIPoma

As NCCN-preferred regimen for symptom and/or tumor control* in individuals** with recurrent or locoregional advanced disease and/or distant metastatic disease if SSTR-positive with any of the following indications:

As a single agent for asymptomatic, low tumor burden and stable disease
As a single agent for symptomatic, clinically significant tumor burden, or clinically significant progression (if not already receiving)
In combination with alternative front-line therapy for symptomatic, clinically significant tumor burden, or clinically significant progression

For symptom and/or tumor control as subsequent therapy at above label dosing after clinical, symptomatic or radiographic progression on standard doses (if SSTR-positive)

NCCN note: *If clinically significant disease progression, treatment with lanreotide (Somatuline® Depot) should be discontinued for nonfunctional tumors and continued in individuals with functional tumors and may be used in combination with any of the subsequent options.
NCCN note: **For individuals with insulinoma, lanreotide (Somatuline® Depot) should be used only if SSTR-based imaging 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.

MANDATES

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of 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.

Guidelines

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

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, lanreotide (Somatuline® Depot) is covered under the medical benefits of the Company’s 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 individuals 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 analogues were created (e.g., lanreotide [Somatuline® Depot]). Somatostatin analogues 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 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 GH and IGF-1 was evaluated in two trials. The first was a three-phase trial that included a 4-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 individuals 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%) of the lanreotide (Somatuline® Depot)–treated individuals had greater than 50% decrease in mean GH from baseline to week four, compared to 0 in the placebo group. In the fixed-dose phase, 72% of the 107 lanreotide (Somatuline® Depot)–treated individuals had a decrease from baseline in mean GH of greater than 50%. 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 4-month fixed-dose phase in which individuals received four deep subcutaneous injections of lanreotide (Somatuline® Depot) at 4-week intervals. This was followed by a dose-titration phase in which 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% (27/63) achieved normal age-adjusted IGF-1 levels, 38% (24/63) individuals achieved both normal IGF-1 levels and GH levels less than or equal to 2.5 ng/mL, and 27% (17/63) had both normal IGF-1 levels and GH levels less than 1 ng/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 2025. Lanreotide. [Lexicomp Online Web site]. 07/29/2025. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 8, 2025.

Colao A, Faggiano A, Pivonello R. Somatostatin analogues: treatment of pituitary and neuroendocrine tumors. Prog Brain Res. 2010;182:281-294.

Elsevier's Gold Standard Clinical Pharmacology Compendium. Lanreotide. 08/06/2025. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed August 8, 2025.

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):184-193.

Lanreotide (Somatuline® Depot)[prescribing information]. Ipsen Biopharmaceuticals, Inc., Cambridge, MA. Available at: Somatuline® Depot (lanreotide) | Home. Updated 07/2024. Accessed August 8, 2025.

Lexi-Drugs Compendium. Lanreotide. 08/06/2025. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 8, 2025.

Ludlam WH, Anthony L. Safety review: dose optimization of somatostatin analogs in patients with acromegaly and neuroendocrine tumors. Adv Ther. 2011;28(10):825-841.

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 August 8, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Neuroendocrine and Adrenal Tumors. V2.2025. 05/28/25 [NCCN Web site.] Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#site [via free subscription]. Accessed August 8, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Lanreotide. [NCCN Web site]. 2025. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=382 [via subscription only]. Accessed August 8, 2025.

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 of carcinoid syndrome&selectedTitle=1~78 [via subscription only]. Accessed August 8, 2025.

Micromedex® Healthcare Series [Internet database]. Lanreotide. 02/27/2025. Greenwood Village, C: ThomsonMicromedex®. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 8, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Lanreotide (Somatuline® Depot) drug label [FDA Web site]. updated 07/2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022074s010lbl.pdf. Accessed August 8, 2025.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J1930 Injection, lanreotide, 1 mg

J1932 Injection, lanreotide (Cipla), 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.01.40h:

11/17/2025

This version of the policy will become effective 11/17/2025.

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 accord

ance with the National Comprehensive Cancer Network (NCCN).

All of the ICD-10 CM codes have been removed from this policy, since they are informational. Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy. Attachment A was removed from the policy.

Revisions From 08.01.40g:

10/01/2024

This policy has been identified for the ICD-10 code update, effective 10/01/2024.

The following ICD-10 code has been removed from Attachment A of this policy:

E34.0 Carcinoid syndrome

The following ICD-10 codes have been added to Attachment A of this policy:

E34.00 Carcinoid syndrome, unspecified
E34.01 Carcinoid heart syndrome
E34.09 Other carcinoid syndrome

Revisions From 08.01.40f:

03/11/2024

This version of the policy will become effective 03/11/2024.

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

The following ICD-10 codes have been added to the coding policy:

C74.90 Malignant neoplasm of unspecified part of unspecified adrenal gland
C74.91 Malignant neoplasm of unspecified part of right adrenal gland
C74.92 Malignant neoplasm of unspecified part of left adrenal gland
C75.5 Malignant neoplasm of aortic body and other

paraganglia

Revisions From 08.01.40e:

10/01/2022

This version of the policy will become effective 10/01/2022

Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS code has been added to this policy:

J1932 Injection,

lanreotide (

cipla), 1 mg

Revisions From 08.01.40d:

06/20/2022

This version of the policy will become effective 06/20/2022

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).

The following ICD- 10 codes have been added to the policy:

C25.0 Malignant neoplasm of head of pancreas
C25.1 Malignant neoplasm of body of pancreas
C25.2 Malignant neoplasm of body of pancreas
C25.3 Malignant neoplasm of body of pancreatic duct
C25.7 Malignant neoplasm of other parts of pancreas
C25.8 Malignant neoplasm of overlapping sites pancreas
C25.9 Malignant neoplasm of pancreas, unspecified
C26.0 Malignant neoplasm of intestinal tract, part unspecified
C26.9 Malignant neoplasm of ill-defined sites within the digestives system

D37.8- Neoplasm of uncertain behavior of other specified digestive organs

D49.0- Neoplasm of unspecified behavior of digestive system

D37.8- Neoplasm of uncertain behavior of other specified digestive organs
D49.0- Neoplasm of unspecified behavior of digestive system

Revisions From 08.01.40c:

03/01/2021

This version of the policy will become effective 03/01/2021.

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).

Revisions From 08.01.40b:

12/30/2019.

Revisions From 08.01.40a:

11/19/2018.

This 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.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

11/17/2025

Version Issued Date:

11/17/2025

Version Reissued Date: