PERJETA, Pertuzumab Form

Pertuzumab (Perjeta®) is a human epidermal growth factor receptor 2 protein (HER2)/neu receptor antagonist. FDA Approved Indication(s) Perjeta is indicated for: • Use in combination with trastuzumab and docetaxel for the treatment of patients with HER2- positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. • Use in combination with trastuzumab and chemotherapy as: o Neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer;
o Adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence. 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 Perjeta is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Diagnosis of HER2-positive breast cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with trastuzumab and one of the following (a, b, or c):
      a. With taxane-containing chemotherapy (e.g. docetaxel or paclitaxel) for the treatment of metastatic breast cancer;
      b. With chemotherapy as neoadjuvant or adjuvant treatment (see Appendix B); c. Member was previously treated with chemotherapy and trastuzumab in absence of Perjeta;
      Prior authorization may be required

2. Request meets one of the following (a or b):* a. Initial dose: 840 mg, followed by maintenance dose: 420 mg every 3 weeks; Page 1 of 7

   CLINICAL POLICY Pertuzumab 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. Additional NCCN Recommended Uses (off-label) (must meet all):

3. Diagnosis of one of the following (a, b or c): a. Recurrent HER2-positive salivary gland tumor; b. Unresectable or metastatic HER2-positive gallbladder cancer or cholangiocarcinoma; c. Advanced or metastatic colorectal cancer and disease is all of the following (i, ii, and iii): i. HER2 positive; ii. Wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use); iii. Wild-type BRAF;
4. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed in combination with trastuzumab;Prior authorization may be required.
5. 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: 6 months C. 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: 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

7. 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.
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   CLINICAL POLICY Pertuzumab II. Continued Therapy A. All Indications in Section I (must meet all):

8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Perjeta for a covered indication and has received this medication for at least 30 days;
9. 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 420 mg every 3 weeks; 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 (total of 18 cycles if neoadjuvant or adjuvant therapy) B. Other diagnoses/indications (must meet 1 or 2):
10. 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

11. 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 Approval duration: Duration of request or 6 months (whichever is less) 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 BRAF: v-raf murine sarcoma viral KRAS: Kirsten rat sarcoma 2 viral oncogene oncogene homolog B1 homologue FDA: Food and Drug Administration HER2: human epidermal growth factor MBC: metastatic breast cancer NRAS: neuroblastoma RAS viral oncogene receptor 2 homologue Page 3 of 7

    CLINICAL POLICY Pertuzumab 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 Examples of drugs that may be used with Perjeta for breast cancer: • Chemotherapeutic agents: carboplatin, cyclophosphamide, doxorubicin, docetaxel, paclitaxel • HER2-targeted agents: trastuzumab (Herceptin®, Kadcyla), lapatinib (Tykerb), Nerlynx® (neratinib)
    • Endocrine therapy: tamoxifen; aromatase inhibitors: anastrozole (Arimidex®), letrozole (Femara®), exemestane (Aromasin®). Regimens are dependent on a variety of factors including menopausal status, treatment/progression history, clinical stage, histology, mutational and receptor status, treatment purpose (e.g., adjuvant and neoadjuvant treatment, treatment for metastatic disease). 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 • Contraindication(s): Known hypersensitivity to pertuzumab or to any of its excipients • Boxed warning(s): Left ventricular dysfunction, embryo-fetal toxicity Maximum Dose See regimens V. Dosage and Administration
    Indication Dosing Regimen Breast cancer Initial dose of 840 mg IV, followed by maintenance dose of 420 mg IV every 3 weeks For metastatic disease, Perjeta should be administered as outlined above. For neoadjuvant treatment, Perjeta should be administered for 3-6 cycles. Following surgery, patients should continue to receive Perjeta to complete 1 year of treatment (up to 18 cycles) For adjuvant treatment, Perjeta should be administered for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity. VI. Product Availability
    Single-dose vial for injection: 420 mg/14 mL Page 4 of 7

    CLINICAL POLICY Pertuzumab VII.