Neratinib (Nerlynx) Form

Neratinib (Nerlynx®) is a kinase inhibitor that irreversibly binds to epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), and HER4. FDA Approved Indication(s) Nerlynx is indicated: • As a single agent, for the extended adjuvant treatment of adult patients with early stage • HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy. In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. 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 Nerlynx is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Diagnosis of breast cancer;
2. Prescribed by or in consultation with an oncologist;
3. Age ≥ 18 years;
4. Disease is HER2-positive;

5. Member meets one of the following (a, b, or c): a. Both (i and ii): i. Documentation of previous adjuvant treatment with trastuzumab (see Appendix B);
   ii. Disease is early stage (stage 1-3) or hormone-receptor positive; b. Prescribed in combination with capecitabine for recurrent, advanced, or metastatic disease, and member has received two or more prior anti-HER2 based regimens used in the metastatic setting; c. Prescribed in combination with capecitabine for central nervous system brain metastases;

   6. For brand Nerlynx requests, member must use generic neratinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
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   Neratinib

   7. Request meets one of the following (a or b): a. Dose does not exceed 240 mg (6 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. 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 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. Breast Cancer (member meets all):
   10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Nerlynx for breast cancer and has received this medication for at least 30 days;
   11. Member is responding positively to therapy;
6. For brand Nerlynx requests, member must use generic neratinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

7. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 240 mg (6 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 Page 2 of 7

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   Neratinib B. Other diagnoses/indications (member meets 1 or 2):

   1. 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
   2. 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 HER: human epidermal growth factor receptor NCCN: National Comprehensive Cancer Network 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 8 mg/kg Herceptin® (trastuzumab) Ogivri™ (trastuzumab- dkst) Ontruzant® (Trastuzumab- dttb) Administer according to one of the following doses and schedules for a total of 52 weeks: Herceptin, Ogivri, Herzuma, Ontruzant, Trazimera, Kanjinti: During and following paclitaxel, docetaxel, or docetaxel/carboplatin:
      • Initial dose of 4 mg/kg as an IV infusion over 90 minutes then at 2 mg/kg as an IV infusion over 30 minutes weekly during chemotherapy for the Page 3 of 7

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   Neratinib Drug Name Dosing Regimen Herzuma® (Trastuzumab- pkrb)
   Trazimera™ (Trastuzumab- qyyp) Kanjinti™ (Trastuzumab- anns) Herceptin Hylecta™ (Trastuzumab- hyaluronidase- oysk) Perjeta® (pertuzumab)
   first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin).
   • One week following the last weekly dose of the trastuzumab product, administer trastuzumab product at 6 mg/kg as an IV infusion over 30 to 90 minutes every 3 weeks.
   Herceptin, Ogivri, Ontruzant, Trazimera, Kanjinti: As a single agent within 3 weeks following completion of multi-modality, anthracycline based chemotherapy regimens:
   • Initial dose: 8 mg/kg as an IV infusion over 90 minutes. • Subsequent doses: 6 mg/kg as an IV infusion over 30 to 90 minutes every 3 weeks Herceptin Hylecta (subcutaneous product): As part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline based therapy: 600 mg trastuzumab and 10,000 units hyaluronidase administered subcutaneously over approximately 2-5 minutes once every 3 weeks for 52 weeks Initial 840 mg IV followed by a maintenance dose of 420 mg IV every 3 weeks for a total of 52 weeks in combination with trastuzumab and either docetaxel or paclitaxel 3.6 mg/kg IV every 3 weeks Dose Limit/ Maximum Dose 600 mg/10,000 units every 3 weeks Maintenance: 420 mg every 3 weeks Kadcyla® (ado- trastuzumab emtansine) Enhertu® (fam- trastuzumab deruxtecan- nxki) 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. 5.4 mg/kg once every 3 weeks 3.6 mg/kg every 3 weeks 5.4 mg/kg every 3 weeks Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Per the Nerlynx prescribing information, antidiarrheal prophylaxis is recommended during the first 56 days of Nerlynx treatment and should be initiated with the first dose of Page 4 of 7

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   Neratinib Nerlynx in order to address the risk of treatment discontinuation due to diarrhea, as was seen in the pivotal ExteNET trial. • Nerlynx is FDA-approved for a one year total duration of therapy as it was only administered for one year in the pivotal ExteNET trial; however, the NCCN does not recommend any specific length of treatment. V. Dosage and Administration Dosing Regimen 240 mg PO QD Indication Breast cancer extended adjuvant treatment Breast cancer advanced, recurrent, or metastatic disease A two-week dose escalation may be considered instead of starting at the 240 mg daily dose for patients with early-stage breast cancer and metastatic breast cancer: week 1 (days 1-7): 120 mg PO QD; week 2 (days 8- 14): 160 mg PO QD. 240 mg PO QD on days 1-21 plus capecitabine 750 mg/m2 PO BID on days 1-14 of a 21-day cycle Maximum Dose 240 mg/day 240 mg/day VI. Product Availability Tablet: 40 mg VII.