ZELBORAF, Vemurafenib Form

Vemurafenib (Zelboraf®) is a kinase inhibitor. FDA Approved Indication(s) Zelboraf is indicated for the treatment of: • Patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test • Patients with Erdheim-Chester disease with BRAF V600 mutation Limitation(s) of use: Zelboraf is not indicated for treatment of patients with wild-type BRAF melanoma. Policy/Criteria Provider must submit documentation (including 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 Zelboraf is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Melanoma (must meet all):

1. Diagnosis of recurrent, lymph node positive, unresectable, or metastatic melanoma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Positive for a BRAF V600 mutation;
   5. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. Request meets one of the following (a or b): a. Dose does not exceed 1,920 mg (8 tablets) 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 Page 1 of 9

   CLINICAL POLICY Vemurafenib B. Histiocytic Neoplasms (must meet all):

3. Diagnosis of one of the following (a or b): a. Erdheim-Chester disease; b. Langerhans cell histiocytosis (off-label);
4. Prescribed by or in consultation with a hematologist or oncologist;
   
   3. Age ≥ 18 years;
   4. Positive for a BRAF V600 mutation;
   5. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
5. Request meets one of the following (a or b): a. Dose does not exceed 1,920 mg (8 tablets) 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. Non-Small Cell Lung Cancer (off-label) (must meet all):
6. Diagnosis of recurrent, advanced, or metastatic non-small cell lung cancer (NSCLC);
   
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Positive for a BRAF V600E mutation;
   5. Failure of Tafinlar® and Mekinist® unless contraindicated or clinically significant adverse effects are experienced;Prior authorization may be required for Tafinlar and Mekinist
7. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
8. 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 D. Hairy Cell Leukemia (off-label) (must meet all):

9. Diagnosis of hairy cell leukemia;

   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Prescribed as one of the following (a, b, or c): a. For members with indications for treatment who are unable to tolerate purine analogs; b. If Zelboraf was not previously given: For those with less than complete response or who relapse within two years of complete response following initial treatment with cladribine or pentostatin; c. Subsequent therapy for relapsed or refractory disease (if not previously given); Page 2 of 9

   CLINICAL POLICY Vemurafenib

10. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. 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. Thyroid Carcinoma (off-label) (must meet all):
12. Diagnosis of progressive or symptomatic differentiated thyroid carcinoma (i.e., papillary, follicular or oncocytic [Hurthle cell] carcinoma);
13. Prescribed by or in consultation with an oncologist;
    
    3. Age ≥ 18 years;
    4. Positive for a BRAF mutation;
    5. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
14. 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 F. Adult Central Nervous System Cancers (off-label) (must meet all):
15. Diagnosis of one of the following (a-h): a. Pilocytic astrocytoma; b. Pleomorphic xanthoastrocytoma (grade 2); c. Ganglioglioma; d. Oligodendroglioma (IDH-mutant, 1p19q codeleted) Grade 2 or 3, when Karnofsky Performance Status ≥ 60; e. Astrocytoma (IDH-mutant) Grade 2, 3, or 4, when Karnofsky Performance Status ≥ 60; f. Glioblastoma; g. Adult low-grade (grade 1) glioma;
16. Brain metastases;Prescribed by or in consultation with an oncologist;
    
    3. Age ≥ 18 years;
    4. Positive for a BRAF V600E mutation;
    5. Prescribed in combination with Cotellic®;
    6. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;

17. 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.
    Page 3 of 9

    CLINICAL POLICY Vemurafenib Approval duration:
    Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less G. Pediatric Central Nervous System Cancers (off-label) (must meet all):

18. Diagnosis of diffuse high-grade glioma unless any of the following (a or b): a. Diffuse midline glioma, H3 K27-altered or pontine location; b. Oligodendroglioma, IDH-mutant, and 1p/19q co-deleted or astrocytoma IDH- mutant;
19. Prescribed by or in consultation with an oncologist;
    
    3. Age ≤ 18 years;
    4. Positive for a BRAF V600E mutation;
    5. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
20. 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 H. Other diagnoses/indications (must meet 1 or 2):
21. 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
22. 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):
23. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zelboraf for a covered indication and has received this medication for at least 30 days;

24. Member is responding positively to therapy; Page 4 of 9

    CLINICAL POLICY Vemurafenib

25. For Zelboraf requests, member must use generic vemurafenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 1,920 mg (8 tablets) 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 (exception: Erdheim-Chester disease).
       Approval duration:
       Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. 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.
    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;
    B. Members with wild-type BRAF disease. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer
    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.
    Page 5 of 9

    CLINICAL POLICY Vemurafenib Drug Name Dosing Regimen Tafinlar (dabrafenib) Mekinist (trametinib) 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. NSCLC: 150 mg PO QD NSCLC: 2 mg PO QD Dose Limit/ Maximum Dose 300 mg/day 2 mg/day Appendix C: Contraindications/Boxed Warnings None reported
    V. Dosage and Administration
    Indication Melanoma, Erdheim- Chester disease VI. Product Availability
    Tablets: 240 mg Dosing Regimen 960 mg PO BID Maximum Dose 1,920 mg/day VII.