Tucatinib (Tukysa) Form

Tucatinib (Tukysa™) is a tyrosine kinase inhibitor with anti-human epidermal growth factor receptor 2 (HER2) activity. FDA Approved Indication(s) Tukysa is indicated:
• In combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting In combination with trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy • This indication is approved under accelerated approval based on tumor response rate and durability of response. Continue approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 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 Tukysa is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Diagnosis of advanced unresectable or metastatic breast cancer;

   2. Confirmation of HER2 positive disease;
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. Failure of one or more anti-HER2 based regimens in the metastatic setting (see Appendix B), unless clinically significant adverse effects are experienced or all are contraindicated;
      *Prior authorization may be required for anti-HER2-based regimens
   6. Prescribed in combination with trastuzumab and capecitabine;
   7. For Tukysa requests, member must use tucatinib, if available, unless contraindicated or clinically significant adverse effects are experienced; Page 1 of 7

   CLINICAL POLICY Tucatinib

2. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): i. 600 mg per day; ii. 4 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 B. Colon Cancer, Rectal Cancer, Appendiceal Adenocarcinoma (must meet all):
3. Diagnosis of advanced, unresectable, or metastatic colon cancer, rectal cancer, or appendiceal adenocarcinoma;
4. Disease is both of the following (a and b): a. HER2 positive (amplified);
   b. RAS (i.e., both KRAS and NRAS) wild-type;
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. No previous use of a HER2 inhibitor therapy (e.g., trastuzumab, Kadcyla®, Tykerb®, Perjeta®);
5. Prescribed in combination with trastuzumab;
   7. One of the following (a or b):
      a. Disease has progressed following a fluoropyrimidine- (e.g., 5-fluorouracil, capecitabine), oxaliplatin-, or irinotecan-based regimen (see Appendix B);
      b. Both of the following (i and ii): i. Disease is BRAF wild-type; ii. Prescribed as initial systemic therapy when intensive therapy is not recommended;
6. For Tukysa requests, member must use tucatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
7. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): i. 600 mg per day;
   ii. 4 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. 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): Page 2 of 7

   CLINICAL POLICY Tucatinib 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 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):
10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tukysa for a covered indication and has received this medication for at least 30 days;
11. Member is responding positively to therapy;
    
    3. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed both of the following (i or ii):
       i. 600 mg per day; ii. 4 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 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):
12. 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

13. 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 Page 3 of 7

    CLINICAL POLICY Tucatinib 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 HER2: human epidermal growth factor NCCN: National Comprehensive Cancer Network receptor 2 NRAS: neuroblastoma rat sarcoma viral KRAS: Kirsten rat sarcoma 2 viral oncogene homologue oncogene homologue 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 and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies
    Breast Cancer
    NCCN examples of systemic therapies for HER2-positive recurrent or metastatic disease
    • Perjeta® (pertuzumab) + Herceptin® (trastuzumab) + Varies Varies Varies docetaxel
    • Perjeta + Herceptin + paclitaxel
    • Enhertu® (fam-trastuzumab deruxtecan-nxki) • Kadcyla® (ado-trastuzumab emtansine) Colorectal Cancer NCCN examples of fluoropyrimidine-, oxaliplatin- and irinotecan-based regimens (not all inclusive):
    • FOLFOX (fluorouracil, leucovorin, and • oxaliplatin) ± bevacizumab (Avastin®, Mvasi®, Zirabev™, Alymsys®, Vegzelma™), Vectibix® (panitumumab), or Erbitux® (cetuximab) • CapeOX (capecitabine and oxaliplatin) ± bevacizumab
    • FOLFIRI (irinotecan, leucovorin, 5-FU) ± bevacizumab, Erbitux, Vectibix, Zaltrap® (ziv-aflibercept), or Cyramza® (ramucirumab) • FOLFOXIRI (irinotecan, oxaliplatin, leucovorin, fluorouracil) ± bevacizumab, Erbitux, or Vectibix
    Page 4 of 7

    CLINICAL POLICY Tucatinib Drug Name Dosing Regimen Dose Limit/ Maximum Dose IROX (oxaliplatin, irinotecan) ± bevacizumab
    • • Bolus or infusional 5-fluorouricil (5-FU) + leucovorin ± bevacizumab • Capecitabine ± bevacizumab
    • Irinotecan ± Erbitux, Vectibix, bevacizumab, Cyramza, or Zaltrap 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
    V. Dosage and Administration
    Indication Breast cancer, colorectal cancer
    Dosing Regimen 300 mg PO BID Maximum Dose 600 mg/day VI. Product Availability
    Tablets: 50 mg, 150 mg VII.