NEXAVAR, Sorafenib Tosylate Form

Sorafenib (Nexavar®) is a kinase inhibitor. FDA Approved Indication(s) Nexavar (sorafenib) is indicated for the treatment of: • Unresectable hepatocellular carcinoma (HCC); • Advanced renal cell carcinoma (RCC); • Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment. 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 Nexavar is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hepatocellular Carcinoma (must meet all):

1. Diagnosis of HCC;
   
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Confirmation of Child-Pugh class A or B7 status;
   5. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
2. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 – 12 months or duration of request, whichever is less B. Renal Cell Carcinoma (must meet all):

3. Diagnosis of advanced, relapsed, or stage IV RCC;

   2. Prescribed by or in consultation with an oncologist; Page 1 of 10

   CLINICAL POLICY Sorafenib

4. Age ≥ 18 years;
   4. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
5. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 – 12 months or duration of request, whichever is less C. Differentiated Thyroid Carcinoma (must meet all):
6. Diagnosis of DTC (includes papillary, follicular, Hürthle cell carcinoma);
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is refractory to radioactive iodine treatment;
   5. Disease is progressive and unresectable, locally recurrent, persistent, or metastatic;
   6. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
7. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 – 12 months or duration of request, whichever is less D. Medullary Thyroid Carcinoma (off-label) (must meet all):
8. Diagnosis of medullary thyroid carcinoma (MTC);
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a or b):
      a. Disease progression on Caprelsa® or Cometriq®, unless clinically significant adverse effects are experienced or both are contraindicated; b. Clinical trials are not available or appropriate; *Prior authorization may be required for Caprelsa and Cometriq
9. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;

10. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 Page 2 of 10

    CLINICAL POLICY Sorafenib Commercial – 12 months or duration of request, whichever is less E. Acute Myeloid Leukemia (off-label) (must meet all):

11. Diagnosis of acute myeloid leukemia;
    2. Prescribed by or in consultation with an oncologist or hematologist;
    3. Age ≥ 18 years;
    4. Disease is FLT3-ITD mutation-positive;
    5. One of the following (a or b): a. Prescribed in combination with azacitidine or decitabine; b. As a single agent for maintenance therapy for member in remission post- allogeneic stem cell transplantation;
12. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
13. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 – 12 months or duration of request, whichever is less F. Bone Cancer (off-label) (must meet all):
14. Diagnosis of one of the following bone cancers (a or b): a. Osteosarcoma, and Nexavar will be used for second-line therapy as a single agent or in combination with everolimus;Prior authorization may be required for everolimus
    b. Chordoma, and Nexavar will be used as single agent therapy for treatment of recurrent disease;
15. Prescribed by or in consultation with an oncologist;
    3. Age ≥ 18 years;
    4. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
16. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 – 12 months or duration of request, whichever is less G. Soft Tissue Sarcoma (off-label) (must meet all):

17. Diagnosis of one of the following soft tissue sarcomas (a, b, c, or d): a. Angiosarcoma as single-agent therapy; b. Desmoid Tumors (aggressive fibromatosis) as single-agent therapy; c. Solitary Fibrous Tumor/Hemangiopericytoma as single-agent therapy; Page 3 of 10

    CLINICAL POLICY Sorafenib d. Gastrointestinal stromal tumors (GIST) with disease progression after single- agent therapy with imatinib, Sutent®, Sprycel ®, Stivarga®, and Qinlock™;Prior authorization may be required for these agents

18. Prescribed by or in consultation with an oncologist;
    3. Age ≥ 18 years;
    4. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
19. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; b. Dose is supported by practice guidelines or peer-reviewed literature (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 H. Ovarian Cancers (off-label) (must meet all):
    
    1. Diagnosis of one of the following (a - f): a. Epithelial ovarian, fallopian tube, or primary peritoneal cancer; b. Clear cell carcinoma of the ovary; c. Mucinous carcinoma of the ovary; d. Carcinosarcoma (malignant mixed Müllerian tumors); e. Low-grade serous carcinoma; f. Grade 1 endometrioid carcinoma;
20. Prescribed by or in consultation with an oncologist;
    3. Age ≥ 18 years;
    4. Disease is platinum-resistant (i.e., cancer returns less than 6 months after finishing platinum-based chemotherapy);
    5. Disease is persistent or recurrent;
    6. Prescribed in combination with topotecan;
    7. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
21. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 – 12 months or duration of request, whichever is less I. Myeloid/Lymphoid Neoplasms (off-label) (must meet all):
22. Diagnosis of lymphoid, myeloid or mixed lineage neoplasms with eosinophilia and FLT3 rearrangement in blast or chronic phase;

23. Prescribed by or in consultation with an oncologist or hematologist;

    3. Age ≥ 18 years; Page 4 of 10

    CLINICAL POLICY Sorafenib

24. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;
25. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per day; 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 - 12 months or duration of request, whichever is less J. Other diagnoses/indications (must meet 1 or 2):
26. 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
27. 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):
28. Currently receiving medication via Centene benefit or documentation supports that member is currently receiving Nexavar for a covered indication and has received this medication for at least 30 days;
29. Member is responding positively to therapy;
    3. For Nexavar requests, member must use sorafenib, unless contraindicated or clinically significant adverse effects are experienced;

30. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 800 mg per day; b. 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 – 12 months Commercial – 12 months or duration of request, whichever is less Page 5 of 10

    CLINICAL POLICY Sorafenib B. Other diagnoses/indications (must meet 1 or 2):

31. 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

32. 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 DTC: differentiated thyroid carcinoma
    FDA: Food and Drug Administration HCC: hepatocellular carcinoma
    MTC: medullary thyroid carcinoma 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 Caprelsa® (vandetanib) MTC: 300 mg PO QD Cometriq® MTC: 140 mg PO QD (cabozantinib) imatinib (Gleevec®) Sutent® (sunitinib) Stivarga® (regorafenib) Qinlock™ (ripretinib) Sprycel® (dasatinib) 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. Soft Tissue Sarcoma: 400 mg PO QD 800 mg/day Soft Tissue Sarcoma: 37.5 to 50 mg PO QD 50 mg/day 160 mg/day Soft Tissue Sarcoma: 160 mg PO QD 150 mg/day GIST: 150 mg PO QD 140 mg/day GIST: 70 mg PO BID Dose Limit/ Maximum Dose 300 mg/day 180 mg/day Page 6 of 10

    CLINICAL POLICY Sorafenib Appendix C: Contraindications/Boxed Warnings
    • Contraindication(s): o Known severe hypersensitivity to sorafenib or any other component of Nexavar o Nexavar use in combination with carboplatin and paclitaxel in patients with squamous cell lung cancer • Boxed warning(s): none reported V. Dosage and Administration
    Indication HCC, RCC, DTC Dosing Regimen 400 mg PO BID Maximum Dose 800 mg/day VI. Product Availability
    Tablet: 200 mg VII.