SUTENT, Sunitinib Malate Form

Sunitinib (Sutent®) is a kinase inhibitor. FDA Approved Indication(s) Sutent is indicated in the treatment of adults with:
• Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate
• Advanced renal cell carcinoma (RCC) • High risk of recurrent RCC following nephrectomy as adjuvant treatment • Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) with unresectable locally advanced or metastatic disease 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 Sutent is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Gastrointestinal Stromal Tumor (must meet all):

1. Diagnosis of GIST;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Request is for one of the following (a, b, or c): a. Disease progression on or intolerance to imatinib (Gleevec®) as a single agent therapy; b. Combination therapy with everolimus for unresectable, recurrent/progressive, or metastatic disease after progression on approved therapies (i.e., imatinib, Qinlock™, Sprycel, Stivarga) (off-label); c. SDH mutation positive disease as a single agent therapy (off-label); *Prior authorization may be required for imatinib.
2. For Sutent requests, member must use generic sunitinib, unless contraindicated or clinically significant adverse effects are experienced;

3. Request meets one of the following (a, b, or c):* a. Dose does not exceed 50 mg per day - 4 weeks on/2 weeks off; Page 1 of 9

   CLINICAL POLICY Sunitinib b. If co-administered with a CYP3A4 inducer (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort): Dose does not exceed 87.5 mg per day - 4 weeks on/2 weeks off c. 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 – 12 months or duration of request, whichever is less B. Renal Cell Carcinoma (must meet all):

4. Diagnosis of RCC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Sutent is requested for (a or b): a. Adjuvant therapy post-nephrectomy for clear cell histology for up to nine 6-week cycles of therapy (one 6-week cycle consists of 4 weeks on/2 weeks off); b. Treatment of relapsed or stage IV RCC;
5. For Sutent requests, member must use generic sunitinib, unless contraindicated or clinically significant adverse effects are experienced;
6. Request meets one of the following (a, b, or c): a. Dose does not exceed 50 mg per day - 4 weeks on/2 weeks off;
   b. If co-administered with a CYP3A4 inducer (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John’s Wort): Dose does not exceed 87.5 mg per day - 4 weeks on/2 weeks off; c. 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 – 12 months or duration of request, whichever is less C. Pancreatic Neuroendocrine Tumor (must meet all):
7. Diagnosis of pNET;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is unresectable, recurrent, advanced, or metastatic;
   5. Prescribed as a single agent;
   6. For Sutent requests, member must use generic sunitinib, unless contraindicated or clinically significant adverse effects are experienced;

8. Request meets one of the following (a. b, or c):* a. Dose does not exceed 37.5 mg per day; b. If co-administered with a CYP3A4 inducer (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort): Dose does not exceed or 62.5 mg per day; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Page 2 of 9

   CLINICAL POLICY Sunitinib *Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less D. NCCN Compendium Indications (off-label) (must meet all):

   1. Diagnosis of one of the following (a, b, c, d, e, f, or g):
      a. Chordoma; b. One of the following soft tissue sarcomas (i, ii, or iii):
      i. Angiosarcoma; ii. Solitary fibrous tumor;
      iii. Alveolar soft part sarcoma;
      c. Thymic carcinoma; d. Differentiated thyroid carcinoma (i.e., papillary carcinoma, follicular carcinoma, Hurthle cell carcinoma) for progressive and/or symptomatic unresectable locoregional recurrent, persistent, or distant metastatic disease not amenable to radioactive iodine (RAI) therapy if clinical trials or other systemic therapies (e.g., Lenvima®, Nexavar®, Cometriq®, Vitravki®, Rozlytrek™, Retevmo™, Keytruda®) are not available or appropriate; Prior authorization may be required. e. Medullary thyroid carcinoma for recurrent or persistent distant metastases if symptomatic disease or progression if clinical trials or preferred systemic therapy options (e.g., Caprelsa®, Cometriq®, Gavreto™, Retevmo™) are not available or appropriate; Prior authorization may be required. f. Myeloid/lymphoid neoplasms with eosinophilia and documentation of FLT3 rearrangement; g. Pheochromocytoma/paraganglioma as primary treatment for secreting tumors as a single agent for locally unresectable disease or distant metastases;
9. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For Sutent requests, member must use generic sunitinib, unless contraindicated or clinically significant adverse effects are experienced;
10. 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 – 12 months or duration of request, whichever is less E. Other diagnoses/indications (must meet 1 or 2):

11. 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 3 of 9

    CLINICAL POLICY Sunitinib 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

12. 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):
13. Currently receiving medication via Centene benefit or documentation supports that member is currently receiving Sutent for a covered indication and has received this medication for at least 30 days;
14. Member is responding positively to therapy;
    3. If receiving adjuvant therapy for RCC, member has not yet received nine 6-week cycles of therapy (one 6-week cycle consists of 4 weeks on/2 weeks off);
15. For Sutent requests, member must use generic sunitinib, unless contraindicated or clinically significant adverse effects are experienced;
16. If request is for a dose increase, request meets one of the following (a, b, or c): a. GIST or RCC (i or ii):
    i. New dose does not exceed 50 mg per day - 4 weeks on/2 weeks off;
    ii. If co-administered with a CYP3A4 inducer (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort): New does does not exceed 87.5 mg per day - 4 weeks on/2 weeks off; b. pNET (i or ii): i. New dose does not exceed 37.5 mg per day; ii. If co-administered with a CYP3A4 inducer (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John’s Wort): New does does not exceed 62.5mg per day; c. Any Indication: New 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 – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

17. 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): Page 4 of 9

    CLINICAL POLICY Sunitinib 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

18. 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 IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration
    GIST: gastrointestinal stromal tumor
    pNET: pancreatic neuroendocrine tumor
    RCC: renal cell carcinoma 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 Dose Limit/ Maximum Dose 800 mg/day GIST: 400 mg/day up to 400 mg BID imatinib mesylate (Gleevec®) Qinlock (ripretinib) Sprycel® (dasatinib) Stivarga® (regorafenib) GIST: 160 mg PO QD for the first 21 days GIST: 150 mg PO QD GIST: 70 mg PO BID 150 mg/day 140 mg/day 160 mg/day Lenvima® (lenvatinib) Differentiated thyroid carcinoma 24 mg/day of each 28-day cycle Nexavar® (sorafenib) 24 mg PO QD Differentiated thyroid carcinoma 400 mg PO BID Caprelsa® (vandetanib) Medullary thyroid carcinoma Cometriq® (cabozantinib) Vitravki® (larotrectinib) Differentiated thyroid carcinoma 300 mg PO QD Medullary thyroid carcinoma 140 mg PO QD 800 mg/day 300 mg/day 140 mg/day 200 mg/day Page 5 of 9

    CLINICAL POLICY Sunitinib Drug Name Dosing Regimen Dose Limit/ Maximum Dose (NTRK fusion-positive): Adult and pediatric patients with body surface area ≥ 1.0 m2: 100 mg PO BID until disease progression or until unacceptable toxicity Pediatric patients with body surface area < 1.0 m2: 100 mg/m2 PO BID until disease progression or until unacceptable toxicity Differentiated thyroid carcinoma (NTRK fusion-positive): Adults: 600 mg PO QD Pediatrics (≥ 12 years of age) by body surface area (BSA): • BSA > 1.50 m2: 600 mg PO QD • BSA 1.11 to 1.50 m2: 500 mg PO QD • BSA 0.91 to 1.10 m2: 400 mg PO QD Thyroid carcinoma (RET-mutant or fusion positive) Weight < 50 kg: 120 mg PO BID
    Weight ≥ 50 kg: 160 mg PO BID
    Differentiated thyroid carcinoma 200 mg IV every 3 weeks OR 400 mg every 6 weeks up to 24 months Thyroid carcinoma (RET-mutant or fusion positive) 400 mg PO QD 600 mg/day See dosing regimen See dosing regimen 800 mg/day with coadministration of strong CYP3A inducers Rozlytrek™ (entrectinib) Retevmo™ (selpercatinib) Keytruda® (pembrolizumab) Gavreto™ (pralsetinib) 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): hepatotoxicity V. Dosage and Administration
    Indication Dosing Regimen GIST
    RCC 50 mg/day PO - 4 weeks/2 weeks off OR 87.5 mg/day PO - 4 weeks on/2 weeks off if co-administered with a CYP3A4 inducer. 50 mg/day PO - 4 weeks/2 weeks off OR 87.5 mg/day PO - 4 weeks on/2 weeks off if co-administered with a CYP3A4 inducer. (Limited to nine 6-week cycles in the adjuvant setting.) Maximum Dose 87.5 mg/day 87.5 mg/day Page 6 of 9

    CLINICAL POLICY Sunitinib Indication Dosing Regimen pNET 37.5 mg/day PO OR 62.5 mg/day PO if coadministered with a CYP3A4 inducer. Maximum Dose 62.5 mg/day VI. Product Availability
    Capsules: 12.5 mg, 25 mg, 37.5 mg, 50 mg
    VII.