Coverage Policy Manual
Policy #: 2018014
Category: Pharmacy
Initiated: April 2018
Last Review: May 2018
  Pharmacy: Lutetium Lu 177 Dotatate (Lutathera®)

Description:
Lutetium Lu 177 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells.
 
Regulatory Status
Lutathera® was FDA-approved in January 2018 for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults (U.S. Food and Drug Administration 2018).

Policy/
Coverage:
 Effective May 2018
 
Effective May 01, 2018, Prior Approval is required for Lutetium Lu 177 Dotate (Lutathera®)
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for the following indications:
 
    • Treatment of well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults when all of the following conditions are met:
 
        1. Tumors must be metastasized or locally advanced, inoperable, and showed disease progression during treatment with a somatostatin analogue (octreotide or lanreotide)  AND
        2. Patients must have a Karnofsky-performance-status score of at least 60 or equivalent (see Rationale).
 
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).
 
Somatostatin Analogs
 
    • Before initiating Lutathera®: long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.   
 
    • During Lutathera® treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.
 
    • Following Lutathera® treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.  
 
Amino Acid Solution
        • Administer IV amino acid solution in accordance with FDA labeling when infusing Lutathera®.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Lutathera® does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, Lutathera® is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
        • For any other indication than those listed above as meeting primary coverage criteria.
        • For any doses that exceed the FDA labeling of 4 dose
        • For patients previously treated with Yttrium-90 or planned comitant treatment with Yttrium-90.
 
Effective Prior to May 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Lutetium Lu 177 dotatate meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness and is covered for the following indications:
 
        • Treatment of well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults when all of the following conditions are met:
 
          1. Tumors must be metastasized or locally advanced, inoperable, and showed disease progression during treatment with a somatostatin analogue (octreotide or lanreotide)  AND
          2. Patients must have a Karnofsky-performance-status score of at least 60 or equivalent (see Rationale).
 
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses (limited to one 4-dose regimen per lifetime).
 
Somatostatin Analogs
 
        • Before initiating Lutathera®: Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutathera®. Administer short-acting octreotide as needed; discontinue at least 24 hours prior to initiating Lutathera®.  
 
        • During Lutathera® treatment: Administer long-acting octreotide 30 mg intramuscularly between 4 to 24 hours after each Lutathera® dose. Do not administer long-acting octreotide within 4 weeks of each subsequent Lutathera® dose. Short-acting octreotide may be given for symptomatic management during Lutathera® treatment, but must be withheld for at least 24 hours before each Lutathera® dose.
 
        • Following Lutathera® treatment: Continue long-acting octreotide 30 mg intramuscularly every 4 weeks after completing Lutathera® until disease progression or for up to 18 months following treatment initiation.  
 
Amino Acid Solution
        • Administer IV amino acid solution containing L-lysine and L-arginine 30 minutes before each dose of Lutathera®.  
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Lutathera® does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, Lutathera® is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
        • For any other indication than those listed above as meeting primary coverage criteria.
        • For any doses that exceed the FDA labeling of 4 dose
        • For patients previously treated with Yttrium-90 or planned comitant treatment with Yttrium-90.

Rationale:
The safety and efficacy of Lutathera® for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has been evaluated in one international multicenter open-label phase 3 trial.
 
Eligible patients were adults who had midgut neuroendocrine tumors that had metastasized or were locally advanced, that were inoperable, that were histologically confirmed and centrally verified, and that showed disease progression on either CT or MRI over the course of a maximum period of 3 years during treatment with octreotide LAR (20 to 30 mg every 3 to 4 weeks for at least 12 weeks before randomization). Patients were required to have a Karnofsky performance-status score of at least 60, have somatostatin receptors present on all target lesions, and have well differentiated histologic features. Well differentiated histologic features defined as a Ki67 index (% of cells that are positive for Ki67 as determined by immunostaining of the primary tumor) of 20% or less.
 
Patients were randomly assigned 1:1 to receive Lutathera® plus best supportive care (n=116), consisting of octreotide long-acting 30 mg every 4 weeks, or high-dose long acting octreotide (n=113), 60 mg every 4 weeks. Median time since diagnosis was 3.8 years in treatment group vs 4.8 years in control group. Ileum (73%) was the primary tumor site.
 
Median progression-free survival not met in treatment group and was 8.4 months in control. (95% CI, 5.8 to 9.1). Data not yet mature to provide median overall survival. At pre-specified analysis 14 deaths in treatment group vs 26 deaths in control group. Estimated risk of death was 60% lower in treatment group. (HR for death (0.40; P = 0.004).
 
Karnofsky Performance Scale
 
The Karnofsky Performance Status Scale classifies patients based on their functional impairment.  The scale ranges from 0 (death) to 100 (normal, no evidence of disease).  
 
The Karnofsky Performance Scale (Karnofsky, 1948)
 
100       Normal; no evidence of disease
90         Able to carry on normal activity; minor signs or symptoms of disease.
80         Normal activity with effort; some signs or symptoms of disease.
70         Cares for self; unable to carry on normal activity or to do active work
60         Requires occasional assistance, but is able to care for most of their personal needs
50         Requires considerable assistance and frequent medical care.
40         Disabled; requires special care and assistance.
30         Severely disabled; hospital admission is indicated although death not imminent.
20         Very sick; hospital admission necessary; active supportive treatment necessary.
10         Moribund; fatal processes progressing rapidly.
0           Death

CPT/HCPCS:
A9513Lutetium lu 177, dotatate, therapeutic, 1 millicurie
A9699Radiopharmaceutical, therapeutic, not otherwise classified
C9031LUTETIUM LU 177 DOTATATE THERAPEUTIC 1 MCI
J3590Unclassified biologics
J9999Not otherwise classified, antineoplastic drugs

References: Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH.(1948) The Use of the Nitrogen Mustards in the Palliative Treatment of Carcinoma – with Particular Reference to Bronchogenic Carcinoma. Cancer. 1948;1(4):634-56.

Colleretto Giacoso (TO) Italy.(2018) Lutathera®® [package insert]. Advanced Accelerator Applications, S.r.l.; 2018

Strosberg, Jonathan, et al.(2017) "Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors." New England Journal of Medicine 376.2 (2017): 125-135.


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.