Pertuzumab/Trastuzumab/Hyaluronidase-zzxf (Phesgo) Form

Pertuzumab/trastuzumab/hyaluronidase-zzxf (Phesgo™) is a fixed-dose subcutaneous formulation of human epidermal growth factor 2 (HER2)/neu receptor antagonists [Perjeta® (pertuzumab) and Herceptin® (trastuzumab)] and endoglycosidase (hyaluronidase). FDA Approved Indication(s) Phesgo is indicated for: • Use in combination with 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. • Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. 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 Phesgo 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 chemotherapy (see Appendix B);
   5. Request meets one of the following (a or b):* a. Dose does not exceed an initial dose of 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase (one single-dose vial), followed by 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase (one single-dose vial) every three weeks;
      b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Page 1 of 6

   CLINICAL POLICY Pertuzumab/Trastuzumab/Hyaluronidase-zzxf *Prescribed regimen must be FDA-approved or recommended by NCCN
   Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer A. Other diagnoses/indications (must meet 1 or 2):

2. 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
3. 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 (must meet all):
4. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Phesgo 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 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase (one single-dose vial) every three 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:
      Medicaid/HIM – 12 months (12 months total [18 cycles] if neoadjuvant or adjuvant therapy) Commercial – 6 months or to the member’s renewal date, whichever is longer
      (12 months total [18 cycles] if neoadjuvant or adjuvant therapy) 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: Page 2 of 6

   CLINICAL POLICY Pertuzumab/Trastuzumab/Hyaluronidase-zzxf 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.
   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 2
   MBC: metastatic breast cancer 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 Varies Examples of drugs that may be used with Phesgo for breast cancer: • Chemotherapeutic agents: carboplatin, cyclophosphamide, doxorubicin • HER2-targeted agents: docetaxel (Taxotere®), paclitaxel • 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. Page 3 of 6

   CLINICAL POLICY Pertuzumab/Trastuzumab/Hyaluronidase-zzxf Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to pertuzumab, or trastuzumab, or hyaluronidase, or to any of its excipients • Boxed warning(s): cardiomyopathy, embryo-fetal toxicity, and pulmonary toxicity
   V. Dosage and Administration
   Maximum Dose See regimens Indication Breast cancer Dosing Regimen Initial dose of 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered SC in the thigh, followed by maintenance dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered SC in the thigh every 3 weeks • For neoadjuvant: administer with chemotherapy by IV infusion preoperatively for 3 to 6 cycles for a total of one year (up to 18 cycles) • For adjuvant: administer with chemotherapy by IV infusion postoperatively for a total of one year (up to 18 cycles) • For metastatic disease: administer with IV infusion of docetaxel Must be administered by a healthcare professional. VI. Product Availability
   Single-dose vial for injection:
   • 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase per 15 mL
   (80 mg, 40 mg, and 2,000 units/mL) • 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase per 10 mL
   (60 mg, 60 mg, and 2,000 units/mL) VII.