Somatostatin Analogs Restricted Product(S)

Corporate Medical Policy: Somatostatin Analogs Restricted Product(s):

• lanreotide (Somatuline® Depot) subcutaneous injection for administration by a healthcare professional • octreotide (Sandostatin®) intravenous infusion or subcutaneous injection for administration by a healthcare professional • *octreotide acetate (Sandostatin® LAR Depot) gluteal intramuscular injection for administration by a healthcare professional • pasireotide (Signifor® LAR) intramuscular injection for administration by a healthcare professional *preferred agent

FDA Approved Use: • Lanreotide (Somatuline® Depot) o For long-term treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy o For treatment of adults with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival o For treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy

• Octreotide (Sandostatin®) o For treatment of acromegaly in patients who have had an inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses o For symptomatic treatment of patients with metastatic carcinoid tumors, to suppress or inhibit severe diarrhea and flushing episodes associated with the disease o For treatment of profuse watery diarrhea associated with Vasoactive Intestinal Peptide (VIP) secreting tumors

• Octreotide (Sandostatin® LAR Depot) o For long-term maintenance treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option o For long-term treatment of severe diarrhea/flushing episodes associated with metastatic carcinoid tumors in patients who have responded to and tolerated octreotide subcutaneous injection

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o For long-term treatment of profuse watery diarrhea associated with Vasoactive Intestinal Peptide (VIP) secreting tumors in patients who have responded to and tolerated octreotide subcutaneous injection

• Pasireotide (Signifor® LAR) o For treatment of acromegaly in patients who have had an inadequate response to surgery and/or for whom surgery is not an option o For treatment of Cushing’s disease in patients for whom pituitary surgery is not an option or has not been curative

Criteria for Medical Necessity: The restricted product(s) may be considered medically necessary when the following criteria are met: Initial Criteria for Approval: 1. The requested medication is pasireotide (Signifor LAR); AND a. The patient has a diagnosis of acromegaly; AND i. The patient has had an inadequate response to pituitary surgery and/or pituitary surgery is not an option; AND ii. The patient has tried and failed or has a contraindication to a somatostatin analog (i.e., octreotide or lanreotide) AND a dopamine agonist (i.e., cabergoline); OR b. The patient has a diagnosis of Cushing’s disease; AND i. Pituitary surgery is not an option or has not been curative; AND ii. The patient has experienced a therapeutic failure or inadequate response to any one of the following oral agents: mitotane, metyrapone, or ketoconazole; OR iii. The patient has a documented intolerance, hypersensitivity, or FDA labeled contraindication to any one of the following agents: mitotane, metyrapone, or ketoconazole; AND c. The patient does not have severe decompensated liver disease (Child-Pugh C); AND d. Signifor LAR has been prescribed by or recommended in consultation with an endocrinologist; OR

2. The requested medication is octreotide (Sandostatin OR Sandostatin LAR Depot); AND a. The patient has a diagnosis of acromegaly; AND i. The use of the requested agent is for adjunctive therapy with pituitary irradiation to alleviate acromegaly symptoms; OR ii. The patient has had an inadequate response to surgical resection or pituitary irradiation defined by ONE of the following documented parameters [medical record documentation required]: 1. Growth hormone level > 5 ng/mL; OR

2. IGF-1 level > 1.9 U/mL for males or > 2.2 U/mL for females; OR iii. The patient is not a candidate for surgical resection or pituitary irradiation; OR b. The patient has a diagnosis of carcinoid tumor, locally advanced/metastatic gastroenteropancreatic neuroendocrine tumor or poorly differentiated (high-grade)/large or small cell neuroendocrine tumor, pancreas islet cell neuroendocrine tumor, or vasoactive intestinal polypeptidoma; AND i. ONE of the following: 1. The patient will be using the medication for symptom control for carcinoid syndrome or hormone hypersecretion; OR 2. The patient has had an inadequate response to or is not a candidate for surgical resection or radiation therapy; OR

3. The requested medication is lanreotide (Somatuline Depot); AND a. The patient has a diagnosis of acromegaly; AND i. The use of the requested agent is for adjunctive therapy with pituitary irradiation to alleviate acromegaly symptoms; OR ii. The patient has had an inadequate response to surgical resection or pituitary irradiation defined by ONE of the following documented parameters [medical record documentation required]: 1. Growth hormone level > 5 ng/mL; OR 2. IGF-1 level > 1.9 U/mL for males or > 2.2 U/mL for females; OR iii. The patient is not a candidate for surgical resection or pituitary irradiation; OR b. The patient has a diagnosis of carcinoid tumor, locally advanced/metastatic gastroenteropancreatic neuroendocrine tumor or poorly differentiated (high-grade)/large or small cell neuroendocrine tumor, pancreas islet cell neuroendocrine tumor, or vasoactive intestinal polypeptidoma; AND i. ONE of the following: 1. The patient will be using the medication for symptom control for carcinoid syndrome or hormone hypersecretion; OR 2. The patient has had an inadequate response to or is not a candidate for surgical resection or radiation therapy; AND c. If the request is for the treatment of acromegaly or carcinoid syndrome, the patient has tried and failed or has an intolerance or contraindication to Sandostatin LAR Depot [medical record documentation required]; AND 4. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below).

Duration of Approval: 180 days (6 months)

Continuation Criteria for Approval:

1. The requested medication is pasireotide (Signifor LAR); AND

a. The patient has been approved through Blue Cross NC initial criteria for approval (above) or would have met initial criteria for approval upon the start of therapy; AND b. The patient is continuing therapy for one of the indications in the initial coverage criteria; AND c. The patient has a diagnosis of acromegaly; AND i. The provider has submitted documentation of improved GH and/or IGF-1 levels [medical record documentation required]; OR d. The patient has a diagnosis of Cushing’s disease; AND i. The provider has submitted documentation of [medical record documentation required]: 1. Reduction in 24-hour urinary free cortisol levels (UFC) showing ≥ 50% reduction from baseline; OR 2. 24-hour urinary free cortisol levels (UFC) are ≤ upper limit of normal; AND/OR 3. Symptomatic improvement of Cushing’s disease; OR

2. The requested medication is octreotide (Sandostatin OR Sandostatin LAR Depot); AND a. The patient has been approved through Blue Cross NC initial criteria for approval (above) or would have met initial criteria for approval upon the start of therapy; AND b. The patient is continuing therapy for one of the indications in the initial coverage criteria; AND c. If the request is for Sandostatin, the patient has been on Sandostatin therapy within the last 180 days (6 months) (NOTE: For patients with a greater than 6-month gap in therapy, use initial coverage criteria); OR d. If the request is for Sandostatin LAR Depot, the patient has been on Sandostatin LAR Depot therapy within the last 180 days (6 months) (NOTE: For patients with a greater than 6-month gap in therapy, use initial coverage criteria; AND e. The patient has objective markers for improvement, exemplified by ONE of the following [medical record documentation required]: i. Growth hormone (GH) level < 5 ng/mL; OR ii. IGF-1 level < 1.9 U/mL for a male or < 2.2 U/mL for a female; OR iii. Clinical improvement in conditions related to the approved diagnosis: 1. Reduction in tumor size; OR 2. Decreased headaches; OR 3. Improved cardiovascular symptoms; OR 4. Improved respiratory symptoms; OR

3. The requested medication is lanreotide (Somatuline Depot); AND a. The patient has been approved through Blue Cross NC initial criteria for approval (above) or would have met initial criteria for approval upon the start of therapy; AND

b. The patient is continuing therapy for one of the indications in the initial coverage criteria; AND c. The patient has been on Somatuline Depot therapy within the last 180 days (6 months) (NOTE: For patients with a greater than 6- month gap in therapy, use initial coverage criteria); AND d. The patient has objective markers for improvement, exemplified by ONE of the following [medical record documentation required]: i. Growth hormone (GH) level < 5 ng/mL; OR ii. IGF-1 level < 1.9 U/mL for a male or < 2.2 U/mL for a female; OR iii. Clinical improvement in conditions related to the approved diagnosis: 1. Reduction in tumor size; OR 2. Decreased headaches; OR 3. Improved cardiovascular symptoms; OR 4. Improved respiratory symptoms; AND

4. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below).

Duration of Approval: 365 days (1 year)

FDA Label Reference Medication Indication Dosing HCPCS Maximum Units* Acromegaly SC: 90 mg every 4 weeks x 3 630 (initial) lanreotide (Somatuline® Depot) months, then adjust dose based on GH and/or IGF-1 1560 (continuation) subcutaneous (SC) injection levels J1930

GEP-NETs SC: 120 mg every 4 weeks 840 (initial)

1560 (continuation)

Carcinoid syndrome SC: 120 mg every 4 weeks 840 (initial) (no additional dosing if patient is already being treated for 1560 (continuation) GEP-NETs)

Acromegaly 50 mcg 3 times daily, may 10080 (initial) octreotide (Sandostatin®) increase dose based on IGF- 1 and GH levels 21900 (continuation) intravenous (IV) infusion, J2354 subcutaneous (SC) injection Common effective dose is 100 mcg 3 times daily, but some patients may require up to 500 mcg 3 times daily for maximum effectiveness

(Note: If increased dose fails to provide additional benefit, dose should be reduced)

Carcinoid tumors 100-600 mcg/day in 2-4 10080 (initial) divided doses for first 2 weeks 21900 (continuation)

Some patients require up to 1500 mcg/day, but there is limited experience with doses exceeding 750 mcg/day

VIP secreting tumors 200-300 mcg/day in 2-4 10080 (initial) divided doses for first 2 weeks, may adjust dose to 21900 (continuation) achieve therapeutic response.

Doses above 450 mcg/day are typically not required

Acromegaly Not currently receiving SC 180 (initial) octreotide (Sandostatin® LAR Sandostatin: Depot) (Start with Sandostatin SC 520 (continuation) formulation 50 mcg 3 times J2353 gluteal intramuscular (IM) daily x 2 weeks) IM: 20 mg injection every 4 weeks for 3 months

Dose may be adjusted based on response, not to exceed 40 mg IM every 4 weeks

Currently receiving SC Sandostatin: IM: 20 mg every 4 weeks x 3 months

Severe diarrhea/flushing associated Not currently receiving SC 180 (initial) with metastatic carcinoid tumors Sandostatin: (Start with Sandostatin SC 520 (continuation) formulation 100-600 mcg/day in 2-4 divided doses x 2 weeks) IM: 20 mg every 4 weeks for 2 months

Dose may be adjusted after 2 months based on symptom control, not to exceed 30 mg IM every 4 weeks

Currently receiving SC Sandostatin: IM: 20 mg every 4 weeks x 2 months

Profuse watery diarrhea associated Not currently receiving SC 180 (initial) with VIP secreting tumors Sandostatin: (Start with Sandostatin SC 520 (continuation) formulation 100-600 mcg/day in 2-4 divided doses x 2 weeks) IM: 20 mg every 4 weeks for 2 months

Dose may be adjusted after 2 months based on symptom control, not to exceed 30 mg IM every 4 weeks

Currently receiving SC Sandostatin: IM: 20 mg every 4 weeks x 2 months

Acromegaly IM: 40 mg every 4 weeks, 280 (initial) pasireotide (Signifor® LAR) then adjust dose based on response and tolerability 520 (continuation) intramuscular (IM) injection J2502 Cushing’s disease IM: 10 mg every 4 weeks, 70 (initial) then adjust dose based on response and tolerability 130 (continuation)

*Maximum units allowed for duration of approval

References: all information referenced is from FDA package insert unless otherwise noted below.

Policy Implementation/Update Information:

April 2021: Criteria change: Added requirement in initial section for Somatuline Depot for trial of or intolerance/contraindication to Sandostatin LAR Depot; adjusted initial length of authorization to 6 months for Signifor LAR; added maximum units; medical policy formatting change. Policy notification given 2/26/2021 for effective date 4/28/2021. *Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy.

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