PORTRAZZA, Necitumumab Form

Necitumumab for injection (Portrazza™) is an epidermal growth factor receptor (EGFR) antagonist. FDA Approved Indication(s) Portrazza is indicated in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC). Limitation(s) of use: Portrazza is not indicated for treatment of non-squamous NSCLC.
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 Portrazza is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-Small Cell Lung Cancer (must meet all):

1. Diagnosis of squamous NSCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with gemcitabine and cisplatin for first-line treatment of metastatic disease;
2. Request meets one of the following (a or b): a. Dose does not exceed 800 mg on days 1 and 8 of each 3-week 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: 6 months B. Other diagnoses/indications (must meet 1 or 2):

3. 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 6

   CLINICAL POLICY Necitumumab
   a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: 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: 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Non-Small Cell Lung Cancer (must meet all):
4. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Portrazza for a covered indication and has received this medication for at least 30 days;
5. 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 800 mg on days 1 and 8 of each 3-week 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: 12 months B. Other diagnoses/indications (must meet 1 or 2):

6. 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: 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: 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: 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 – HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents.
      Page 2 of 6

   CLINICAL POLICY Necitumumab
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key EGFR: epidermal growth factor receptor
   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.
   Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies gemcitabine; cisplatin
   Examples of Portrazza/gemcitabine/cisplatin dosing regimens: • Portrazza pivotal trial: o Patients were randomly assigned to gemcitabine 1250 mg/m2 IV days 1 and 8, cisplatin 75 mg/m2 IV day 1 +/- Portrazza 800 mg IV days 1 and 8. • Clinical Pharmacology: o Adults: NSCLC (inoperable, locally advanced, or metastatic):
    Gemcitabine 1,000 mg/m2 IV over 30 minutes followed by cisplatin 100 mg/m2 IV on day 1, then gemcitabine 1,000 mg/m2 IV over 30 minutes on days 8 and 15, repeated every 4 weeks.
    Alternatively, gemcitabine 1,250 mg/m2 IV over 30 minutes followed by cisplatin 100 mg/m2 IV on day 1, then gemcitabine 1,250 mg/m2 IV over 30 minutes on day 8, repeated every 3 weeks. 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/Black Box Warnings • Contraindications: none reported • Black box warnings: cardiopulmonary arrest and hypomagnesemia Appendix D: General Information • The NCCN NSCLC Panel voted unanimously to delete the Portrazza/cisplatin/gemcitabine regimen from the NCCN Guidelines for patients with metastatic squamous cell NSCLC. This decision reflects the fact that the NCCN NSCLC Panel feels the addition of Portrazza to the regimen is not beneficial based on toxicity, cost, and limited improvement in efficacy when compared with cisplatin/gemcitabine. A phase 3 randomized trial only showed a slight improvement in overall survival (11.5 vs Page 3 of 6

   CLINICAL POLICY Necitumumab
   9.9 months). In addition, there were more grade 3 or higher adverse events in patients receiving the Portrazza regimen. V. Dosage and Administration
   Indication Squamous NSCLC Dosing Regimen 800 mg as an IV infusion over 60 minutes on Days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion. Maximum Dose 800 mg per infusion VI. Product Availability
   Single-dose vial: 800 mg/50 mL (16 mg/mL) VII.