SANDOSTATIN, Octreotide Acetate SANDOSTATIN LAR DEPOT, Octreotide Acetate Form

Octreotide acetate (Sandostatin® Injection, Sandostatin® LAR Depot, Mycapssa®) is a somatostatin analog. ____ *For Health Insurance Marketplace (HIM), if request is through pharmacy benefit, Mycapssa is non-formulary and should not be approved using these criteria; refer to the formulary exception policy, HIM.PA.103.
FDA Approved Indication(s) Sandostatin Injection is indicated for:
• Acromegaly o To reduce blood levels of growth hormone (GH) and insulin-like growth factor (IGF-I) (somatomedin C) in acromegaly patients who have had inadequate response or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses; • Carcinoid tumors o For the symptomatic treatment of patients with metastatic carcinoid tumors where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease • Vasoactive intestinal peptide tumors (VIPomas) o For the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide (VIP)-secreting tumors Sandostatin LAR Depot is indicated for treatment in patients who have responded to and tolerated Sandostatin Injection subcutaneous injection for: • Acromegaly • Carcinoid tumors
o Severe diarrhea/flushing episodes associated with metastatic carcinoid tumors • Vasoactive intestinal peptide tumors (VIPomas) o Profuse watery diarrhea associated with VIP-secreting tumors Mycapssa is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide. Limitation(s) of use: In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and Sandostatin LAR Depot on tumor size, rate of growth and development of metastases, has not been determined. Page 1 of 11

CLINICAL POLICY Octreotide Acetate Policy/Criteria Provider must submit documentation (including such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Sandostatin Injection, Mycapssa, and Sandostatin LAR Depot are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acromegaly (must meet all):

1. Diagnosis of acromegaly as evidenced by one of the following (a or b): a. Pre-treatment IGF-I level above the upper limit of normal based on age and gender for the reporting laboratory; b. Serum GH level ≥ 1 µg/mL after a 2-hour oral glucose tolerance test;
2. Prescribed by or in consultation with an endocrinologist;
   3. Age ≥ 18 years or, if younger, epiphyseal growth plates have closed;
   4. One of the following (a or b):
      a. Inadequate response to surgical resection or pituitary irradiation (i.e., unable to achieve normalization of GH and/or IGF-I levels or unable to adequately control tumor mass) b. Member is not a candidate for surgical resection or pituitary irradiation;
   5. For Sandostatin injection, member must use generic octreotide acetate, unless contraindicated or clinically significant adverse effects are experienced;
3. For Sandostatin LAR requests, member has received Sandostatin Injection for at least two weeks with improvement in GH or IGF-I levels, or tumor mass control;
   7. For Mycapssa requests, member has responded to and tolerated treatment with octreotide or lanreotide;

4. Dose does not exceed any of the following (Sandostatin Injection can be used with Sandostatin LAR Depot) (a, b, or c): a. Sandostatin Injection: 1,500 mcg per day in divided doses; b. Sandostatin LAR Depot: 40 mg every 4 weeks; c. Mycapssa: 80 mg (4 capsules) per day; Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 6 months or to the member’s benefit renewal date, whichever is longer B. Carcinoid Tumor (Neuroendocrine Tumor of the Gastrointestinal Tract, Lung and Thymus) (must meet all):

   1. Request is for Sandostatin Injection or Sandostatin LAR Depot;
   2. Diagnosis of a carcinoid tumor (most commonly arising in the lungs and bronchi, small intestine, appendix, rectum, or thymus) and one of the following (a or b): a. Request is for carcinoid syndrome (i.e., presence of diarrhea or flushing symptoms indicative of hormonal hypersecretion); b. Request is for advanced disease, with or without carcinoid syndrome; Page 2 of 11

   CLINICAL POLICY Octreotide Acetate

5. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. For Sandostatin injection, member must use generic octreotide acetate, unless contraindicated or clinically significant adverse effects are experienced;
6. For Sandostatin LAR Depot requests, if request is for symptom management only, member has received Sandostatin Injection for at least two weeks with improvement in diarrhea or flushing episodes;
7. Request meets one of the following (Sandostatin Injection can be used with Sandostatin LAR Depot) (a or b): a. Dose does not exceed any of the following (i or ii):
   i. Sandostatin Injection: 1,500 mcg per day in divided doses; ii. Sandostatin LAR Depot: 30 mg every 4 weeks; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 6 months or to the member’s benefit renewal date, whichever is longer C. Pancreatic Neuroendocrine Tumor (including VIPoma) and Adrenal Tumor (must meet all):
   1. Request is for Sandostatin Injection or Sandostatin LAR Depot;
   2. Diagnosis of one of the following (a or b): a. Pancreatic neuroendocrine tumor including but not limited to VIPoma, gastrinoma, insulinoma or glucagonoma, and one of the following (i, ii, iii, or iv): i. Request is for management of symptoms indicative of hormonal hypersecretion (e.g., diarrhea); ii. Request is for treatment of a gastrinoma with or without symptoms; iii. For other pancreatic neuroendocrine tumors, request is for advanced disease, with or without symptoms; iv. If request is for an insulinoma, tumor is somatostatin receptor positive on imaging; b. Advanced adrenal pheochromocytoma/paraganglioma;
8. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. For Sandostatin injection, member must use generic octreotide acetate, unless contraindicated or clinically significant adverse effects are experienced;
9. For Sandostatin LAR Depot requests, if request is for symptom management only, member has received Sandostatin Injection for at least two weeks with improvement in symptoms;

10. Request meets one of the following (Sandostatin Injection can be used with Sandostatin LAR Depot) (a or b):*
    a. Dose does not exceed any of the following (i or ii):
    i. Sandostatin Injection: 750 mcg per day in divided doses; ii. Sandostatin LAR Depot: 30 mg every 4 weeks; Page 3 of 11

    CLINICAL POLICY Octreotide Acetate b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    Medicaid/HIM – 6 months Commercial – 6 months or to the member’s benefit renewal date, whichever is longer D. Meningioma (off-label) (must meet all):

11. Request is for Sandostatin Injection or Sandostatin LAR Depot;
    
    2. Diagnosis of meningioma (cancer of the central nervous system);
    3. Prescribed by or in consultation with an oncologist;
    4. Age ≥ 18 years;
    5. For Sandostatin injection, member must use generic octreotide acetate, unless contraindicated or clinically significant adverse effects are experienced;
12. Disease is not amenable to surgery or radiation;
    7. Octreotide scan is positive;
    8. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
       Medicaid/HIM – 6 months Commercial – 6 months or to the member’s benefit renewal date, whichever is longer E. Thymoma and Thymic Carcinoma (off-label) (must meet all):
13. Request is for Sandostatin Injection or Sandostatin LAR Depot;
    
    2. Diagnosis of thymoma or thymic carcinoma;
    3. Prescribed by or in consultation with an oncologist;
    4. Age ≥ 18 years;
    5. For Sandostatin injection, member must use generic octreotide acetate, unless contraindicated or clinically significant adverse effects are experienced;
14. Octreotide scan or dotatate PET/CT is positive;
    
    7. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
       Medicaid/HIM – 6 months Commercial – 6 months or to the member’s benefit renewal date, whichever is longer F. Other diagnoses/indications (must meet 1 or 2):

15. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 4 of 11

    CLINICAL POLICY Octreotide Acetate CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

16. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. Acromegaly (must meet all):
17. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
18. Member is responding positively to therapy (e.g., improvement in GH or IGF-1 serum concentrations, or in tumor mass control, since initiation of therapy);
    3. If request is for a dose increase, new dose does not exceed any of the following (Sandostatin injection can be used with Sandostatin LAR Depot ) (a, b, or c): a. Sandostatin Injection: 1,500 mcg per day in divided doses; b. Sandostatin LAR Depot: 40 mg every 4 weeks; c. Mycapssa: 80 mg (4 capsules) per day. Approval duration:
       Medicaid/HIM – 6 months Commercial – 6 months or to the member’s benefit renewal date, whichever is longer B. Carcinoid Tumor and Pancreatic/Adrenal Neuroendocrine Tumor (must meet all):
    4. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Sandostatin Injection or Sandostatin LAR Depot for a covered indication and has received this medication for at least 30 days;

19. Request is for Sandostatin Injection or Sandostatin LAR Depot;

    3. Member is responding positively to therapy;
    4. If request is for a dose increase, request meets one of the following (Sandostatin Injection can be used with Sandostatin LAR Depot ) (a or b):* a. New dose does not exceed one of the following (i or ii):
       i. Sandostatin Injection (1 or 2):
       1) Carcinoid tumors: 1,500 mcg per day in divided doses; 2) VIPomas: 750 mcg per day in divided doses; ii. Sandostatin LAR Depot: 30 mg every 4 weeks; Page 5 of 11

    CLINICAL POLICY Octreotide Acetate b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    Medicaid/HIM – 6 months Commercial – 6 months or to the member’s benefit renewal date, whichever is longer C. Meningioma, Thymoma and Thymic Carcinoma (off-label) (must meet all):

20. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Sandostatin Injection or Sandostatin LAR Depot for a covered indication and has received this medication for at least 30 days;
21. Request is for Sandostatin Injection or Sandostatin LAR Depot;
    
    3. Member is responding positively to therapy;
    4. If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
       Medicaid/HIM – 6 months Commercial – 6 months or to the member’s benefit renewal date, whichever is longer D. Other diagnoses/indications (must meet 1 or 2):
22. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

23. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents. Page 6 of 11

    CLINICAL POLICY Octreotide Acetate IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration GH: growth hormone IGF-I: insulin growth factor I (somatomedin C) Appendix B: Therapeutic Alternatives
    Not applicable NCCN: National Comprehensive Cancer Network VIPoma: vasoactive intestinal peptide tumor Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Sandostatin Injection and Mycapssa: hypersensitivity to this drug or any of its components o Sandostatin LAR Depot: none reported • Boxed warning(s): none reported Appendix D: General Information
    Acromegaly: GH excess occurring in growing children/adolescents before epiphyseal growth plate closure (known as pituitary gigantism) is not included in the present policy given unique etiologic and management considerations. V. Dosage and Administration
    Drug Name octreotide acetate (Sandostatin Injection) (SC or IV) octreotide acetate (Sandostatin LAR Depot) (IM) Mycapssa (octreotide acetate) Indication Dosing Regimen Acromegaly Up to 1,500 mcg in 2 or more divided doses Up to 1,500 mcg in 2 or more divided doses Up to 750 mcg in 2 or more divided doses Carcinoid tumors VIPomas Acromegaly 20-40 mg every 4 weeks
    20-30 mg every 4 weeks Carcinoid tumors VIPomas Acromegaly 20-30 mg every 4 weeks Initial: 20 mg PO BID. Titrate based on IGF-1 levels and patient’s signs and symptoms. Increase dose in 20 mg increments to a maximum of 40 mg PO QD Maximum Dose 1,500 mcg/day 1,500 mcg/day 750 mcg/day 40 mg/4 weeks 30 mg/4 weeks 30 mg/4 weeks 80 mg/day Page 7 of 11

    CLINICAL POLICY Octreotide Acetate VI. Product Availability
    Drug Name octreotide acetate (Sandostatin Injection) octreotide acetate (Sandostatin LAR Depot) Mycapssa (octreotide acetate) Availability Single-use ampules: 50 mcg/mL, 100 mcg/mL, 500 mcg/mL Multi-dose vials: 200 mcg/mL, 1,000 mcg/mL Single-use kit (vials): 10 mg, 20 mg, 30 mg Delayed-release capsule: 20 mg VII.