Coverage Policy Manual
Policy #: 2017033
Category: Pharmacy
Initiated: October 2017
Last Review: October 2018
  Octreotide Acetate for Injectable Suspension (Sandostatin® LAR Depot)

Description:
Octreotide is a somatostatin analogue believed to work at the somatostatin receptor that inhibits the secretion of both pituitary and gastrointestinal hormones including serotonin, gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, pancreatic polypeptide, growth hormone, and thyrotropin. This results in increased intestinal absorption of water and electrolytes, decreased pancreatic and gastric acid secretions, and increased intestinal transit time.
 
Octreotide was FDA-approved for the treatment of carcinoid tumors and VIPomas n October 1988 and    was FDA-approved for the treatment of acromegaly in June 1995. The FDA approved a long-acting dosage form of octreotide, Sandostatin LAR® Depot, for the treatment of acromegaly and to control the symptoms of carcinoid tumors and VIPomas in patients that respond to and tolerate initial treatment with subcutaneous octreotide in November 1998. (Clinical Pharmacology, 2017)

Policy/
Coverage:
Effective October 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Octreotide acetate for injectable suspension (Sandostatin® LAR) meets primary coverage criteria and is covered for the following conditions:
  
  1. For the long-term maintenance therapy in acromegalic patients who meet all of the following criteria:
 
A. Diagnosis of acromegaly confirmed by both of the following:
      • Serum GH level > 1 ng/mL after a 2 hour oral glucose tolerance test (OGTT) at time of diagnosis
      • Elevated serum IGF-1 levels (above the age and gender adjusted normal range as provided by the physician’s lab) at time of diagnosis; AND
B. Patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.
 
2. For the long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.
 
3. For the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) when there is supporting documentation that the patient has responded to octreotide injections (short acting) for 4 weeks or greater.
 
4. For second-line therapy for diarrhea (chemotherapy or radiation induced diarrhea) that is unresponsive to conventional antidiarrheal medications (for example, diphenoxylate and atropine or loperamide) and has demonstrated a clinically significant response to short acting octreotide for at least 4 weeks.
 
5. NCCN 1, 2A and 2B Recommendations in accordance with Coverage Policy #2000030
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of octreotide for any indication not listed above as covered, does not meet primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of octreotide for any indication not listed above as covered is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to October 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Octreotide acetate for injectable suspension meets primary coverage criteria and is covered for the following conditions:
 
Acromegaly
 
1. For long-term maintenance therapy in acromegalic patients who meet all of the following criteria:
 
A. Diagnosis of acromegaly confirmed by both of the following:
        • Serum GH level > 1 ng/mL after a 2 hour oral glucose tolerance test (OGTT) at time of diagnosis
        • Elevated serum IGF-1 levels (above the age and gender adjusted normal range as provided by the physician’s lab) at time of diagnosis; AND
B. Patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option.
 
 
Neuroendocrine tumors
 
1. For the long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors, as a single agent or in combination with telotristat
 
2. For neuroendocrine tumors of the adrenal gland as symptom control when all of the following criteria are met:
a.. somatostatin receptor scintigraphy is positive and
          • patients has non-adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome and
          • tumors are less than 4 cm and
          • cortisol production is symmetrical
b. For neuroendocrine tumors of the pancreas and one of the following:
          • For the treatment of symptoms related to hormone hypersecretion; (Note: if disease progression, treatment with octreotide may be continued in combination with any of the subsequent treatment options)
          • For tumor control in patients with unresectable locoregional disease and/or metastatic disease and clinically significant tumor burden or clinically significant progression if not already given
c. For primary treatment of unresected primary gastrinoma
d. For neuroendocrine tumors of the GI tract, lung, and thymus for unresectable disease and/or distant metastases  (Note: if disease progression, treatment with octreotide may be continued in combination with any of the subsequent treatment options)
 3. For the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) when   there is supporting documentation that the patient has responded to octreotide injections (short acting) for 4 weeks or greater.
 
Thymomas and Thymic Carcinomas
 
1. As second-line therapy for the treatment of thymomas and thymic carcinomas
 
Meningiomas
 
  1. As treatment for surgically inaccessible recurrent or progressive meningiomas when further radiation is not possible
 
Chemotherapy or Radiation-induced Diarrhea
 
1. For second-line therapy for diarrhea that is unresponsive to conventional antidiarrheal medications (for example, diphenoxylate and atropine or loperamide) and has demonstrated a clinically significant response to short acting octreotide for at least 4 weeks.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of octreotide for any indication not listed above as covered, does not meet primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of octreotide for any indication not listed above as covered is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 

Rationale:
Acromegaly
In clinical trials of Sandostatin LAR Depot were performed in patients who had been receiving Sandostatin Injection for a period of weeks to as long as 10 yrs.  The acromegaly studies with Sandostatin LAR Depot were performed in patients who achieved GH levels of <10 ng /ml (and in most cases <5 ng/ml) while on sub q Sandostatin Injections.  However, some patients enrolled were partial responders to sub q Sandostatin Injection, i.e., GH levels were reduced by >50% on sub q Sandostatin Injection compared to the untreated state, although not suppressed to <5 ng/ml.  
In all three trials, GH, IGF-1 and clinical symptoms were similarly controlled on Sandostatin LAR Depot as they had been on Sandostatin Injection.  
Of the 25 patients who completed the trials and were partial responders to Sandostatin Injection (GH >5.0 ng/ml but reduced by >50% relative to untreated levels), 1 patient (4%) responded to Sandostatin LAR Depot with a reduction of GH to <2.5 ng/mL and 8 patients (32%) responded with a reduction of GH to <5.0 ng/mL.  
Two open label clinical studies investigated a 48-week treatment with Sandostatin LAR Depot in 143 untreated (de novo) acromegalic patients.  The median reduction in tumor volume was 20.6% in Study 1 (49 patients) at 24 weeks and 24.5% in Study 2 (94 patients) at 24 weeks and 36.2% at 48 weeks.  
 
Carcinoid Syndrome
A 6-month clinical trial of malignant carcinoid syndrome was performed in 93 patients who had previously been shown to be responsive to Sandostatin Injection.  67 patients were randomized at baseline to receive double-blind doses of 10 mg, 20mg, or 30 mg Sandostatin LAR Depot every 28 days and 26 patients continued, unblinded, on their previous Sandostatin Injection regimen (100-300 mcg three times daily).  
Overall, mean daily stool frequency was as well controlled on Sandostatin LAR Dpot as on Sandostatin Injection (approximately 2-2.5 stools/day).
Mean daily flushing episodes were similar at all doses of Sandostatin LAR Depot and on Sandostatin Injection (approximately 0.5-1 episode/day).
In a subset of patients with variable severity of disease median 24 hour urinary 5-HIAA (5-hydroxyindole acetic acid) levels were reduces by 38% - 50% in the groups randomized to Sandostatin LAR Depot.  
78 patients with malignant carcinoid syndrome, who had participated in this 6-month trial, subsequently participated in a 12-month extension study in which they received 12 injections of Sandostatin LAR Depot at 4-week intervals.  For those who remained in the extension trial, diarrhea and flushing were as well controlled as during the 6-month trial.   Because malignant carcinoid disease is progressive, as expected, a number of deaths (8 patients: 10%) occurred due to disease progression or complications from the underlying disease.  An additional 22% of patients prematurely discontinued Sandostatin LAR Depot due to disease progression or worsening carcinoid symptoms.  

CPT/HCPCS:
J2353Injection, octreotide, depot form for intramuscular injection, 1 mg

References: Octreotide. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. c2017- [cited 2017 August 2]. Available from: http://www.clinicalpharmacology.com

Sandostatin LAR® [package insert]. East Hanover, New Jersey: Novartis Pharmaceuticals Corporation.; 2016

U.S. Food & Drug Administration. Sandostatin LAR® [package insert]. https://www.fda.gov/search. Accessed August 2, 2017.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.