LUTATHERA, Lutetium Lu 177 Dotatate Form

Lutetium Lu 177 dotatate (Lutathera®) is a radiolabeled somatostatin analog. FDA Approved Indication(s) Lutathera is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut NETs in adults. Policy/Criteria Provider must submit documentation (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 Lutathera is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Neuroendocrine Tumors (must meet all):

1. Diagnosis of a somatostatin receptor-positive NET of one of the following origins (a or b): a. Gastrointestinal tract or pancreas; b. Lung or thymus (off-label);
2. Prescribed by or in consultation with an oncologist;
   
   3. Age ≥ 18 years;
   4. Disease is metastatic or locally advanced, and unresectable;
   5. Member experienced disease progression while on a somatostatin analog (e.g., octreotide, lanreotide);
3. Dose does not exceed 7.4 GBq (200 mCi) every 8 weeks, up to a total of 4 doses. Approval duration: 32 weeks (no more than 4 total doses)
   B. Pheochromocytoma/Paraganglioma (off-label) (must meet all):

4. Diagnosis of a somatostatin receptor-positive pheochromocytoma/paraganglioma;

   2. Prescribed by or in consultation with an oncologist;
   3. Disease is metastatic or locally advanced, and unresectable;
   4. Dose does not exceed 7.4 GBq (200 mCi) every 8 weeks, up to a total of 4 doses. Approval duration: 32 weeks (no more than 4 total doses) Page 1 of 6

   CLINICAL POLICY Lutetium Lu 177 Dotatate C. Other diagnoses/indications (must meet 1 or 2):

5. 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
6. 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. All Indications in Section I (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Lutathera for a covered indication;
8. Member is responding positively to therapy;
   
   3. Member has not received ≥ 4 doses of Lutathera;
   4. If request is for a dose increase, new dose does not exceed 7.4 GBq (200 mCi) every 8 weeks, up to a total of 4 doses.
      Approval duration: 32 weeks (no more than 4 total doses) B. Other diagnoses/indications (must meet 1 or 2):
9. 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

10. 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.
    Page 2 of 6

    CLINICAL POLICY Lutetium Lu 177 Dotatate 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.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CT: computed tomography FDA: Food and Drug Administration GEP-NET: gastroenteropancreatic neuroendocrine tumor mCi: millicurie NCCN: National Comprehensive Cancer Network
    Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen 90 – 120 mg SC every 4 weeks Somatuline® Depot (lanreotide) Sandostatin® LAR Depot (octreotide LAR) Sandostatin® (octreotide)
    Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label for the treatment of NETs (octreotide is only FDA-approved for the treatment of symptoms associated with carcinoid tumors) – NET dosing recommendations are per the NCCN guidelines
    20 – 30 mg IM once monthly (20 mg may be used for pancreatic NETs) 150 – 250 mcg SC TID
    30 mg/month 450 mcg/day Dose Limit/ Maximum Dose 120 mg/month Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Somatostatin receptor expression can be detected by somatostatin receptor-based imaging, which includes 68Ga-dotatate PET/CT (preferred per the NCCN) and somatostatin receptor scintigraphy. • Use of Lutathera with somatostatin analogs: o Before initiating Lutathera: Long-acting somatostatin analogs (e.g., long-acting octreotide) should be discontinued for at least 4-6 weeks prior to initiation of Lutathera. Short-acting octreotide can be administered as needed up to 24 hours prior to initiating Lutathera. o After Lutathera: Administer long-acting octreotide 30 mg intramuscularly 4 to 24 hours after each Lutathera dose and short-acting octreotide for symptomatic management. o 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. Page 3 of 6

    CLINICAL POLICY Lutetium Lu 177 Dotatate o During Lutathera treatment: IV infusion of amino acids is critical for nephron protection and should be infused 30 minutes before and 3 hours after Lutathera treatment
    o Following Lutathera treatment: Octreotide or lanreotide (short and long acting) can be administered 4 to 24 hours after completing Lutathera.
    V. Dosage and Administration
    Indication GEP-NET NET of lung or thymus origin, pheochromocytoma, paragangliomaOff-label – dosing recommendations are per the NCCN guidelines Dosing Regimen 7.4 GBq (200 mCi) IV every 8 weeks for a total of 4 doses Maximum Dose 7.4 BGq (200 mCi) IV (4 doses) VI. Product Availability
    Single-dose vial for injection: 370 MBq/mL (10 mCi/mL)
    VII.