Tivozanib (Fotivda) Form

Tivozanib (Fotivda®) is a tyrosine kinase inhibitor. FDA Approved Indication(s) Fotivda is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. 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 Fotivda is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Renal Cell Carcinoma (must meet all):

1. Diagnosis of advanced RCC with clear cell histology;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is relapsed or refractory following at least 2 prior systemic therapies (see Appendix B);
2. For brand Fotivda requests, member must use generic tivozanib, if available, unless contraindicated or clinically significant adverse effects are experienced;
3. Request meets one of the following (a or b): a. Dose does not exceed 1.34 mg per day for 21 days, followed by 7 days off treatment, for every 28-day cycle; 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. Other diagnoses/indications (must meet 1 or 2):

4. 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 1 of 5

   CLINICAL POLICY Tivozanib 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

5. 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. Renal Cell Carcinoma (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Fotivda for a covered indication and has received this medication for at least 30 days;
7. Member is responding positively to therapy;
   3. For brand Fotivda requests, member must use generic tivozanib, 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 1.34 mg per day for 21 days, followed by 7 days off treatment, for every 28-day cycle; 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 B. Other diagnoses/indications (must meet 1 or 2):
8. 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

9. 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 Page 2 of 5

   CLINICAL POLICY Tivozanib 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 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 Varies Dose Limit/ Maximum Dose Varies Inlyta (axitinib) + Bavencio® (avelumab) Regimens for clear cell histology: Inlyta® (axitinib) + Keytruda® (pembrolizumab) • • Cabometyx® (cabozanitinib) + Opdivo® (nivolumab) • Lenvima® (lenvatinib) + Keytruda (pembrolizumab) • Votrient® (pazopanib) • Sutent® (sunitinib) • Yervoy® (ipilumab) + Opdivo (nivolumab) • Cabometyx (cabozanitinib)
   • • Proleukin® (aldesleukin) • Torisel® (temsirolimus) • Opdivo (nivolumab) • Lenvima (lenvatinib) + Afinitor® (everolimus) • Avastin® (bevacizumab) • Nexavar® (sorafenib) • Inlyta (axitinib) 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 None reported Page 3 of 5

   CLINICAL POLICY Tivozanib V. Dosage and Administration
   Indication Dosing Regimen RCC 1.34 mg PO QD for 21 days on treatment followed by 7 days off treatment (28-day cycle) until disease progression or unacceptable toxicity
   Maximum Dose 1.34 mg/day Reduce the dose to 0.89 mg/day for patients with moderate hepatic impairment VI. Product Availability
   Capsules: 1.34 mg, 0.89 mg VII.