KADCYLA, Ado-Trastuzumab Emtansine Form

Ado-trastuzumab emtansine (Kadcyla®) is a human epidermal growth factor receptor 2 protein (HER2)-targeted antibody and microtubule inhibitor conjugate. FDA Approved Indication(s) Kadcyla is indicated as a single agent for the: • Adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. • Treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
o Received prior therapy for metastatic disease, or
o Developed disease recurrence during or within six months of completing adjuvant therapy.
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 Kadycla 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 as a single agent;
   5. Documentation of prior use of trastuzumab-based therapy and a taxane;
   6. Request meets one of the following (a, b, or c): a. As adjuvant: Dose does not exceed 3.6 mg/kg every 21 days for a maximum of 14 doses; b. For metastatic: Dose does not exceed 3.6 mg/kg every 21 days; c. 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 Page 1 of 6

   CLINICAL POLICY Ado-Trastuzumab Emtansine Commercial – 6 months or to the member’s renewal date, whichever is longer B. Additional NCCN Recommended Uses (off-label) (must meet all):

2. Diagnosis of one of the following (a or b): a. Recurrent, advanced, or metastatic HER2-positive non-small cell lung cancer (NSCLC); b. Recurrent HER2-positive salivary gland tumor;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed as a single agent;
   5. Request meets one of the following (a or b): a. Dose does not exceed 3.6 mg/kg every 21 days; 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 – 6 months or to the member’s renewal date, whichever is longer C. 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): 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
4. 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):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Kadcyla for a covered indication and has received this medication for at least 30 days;

6. Member is responding positively to therapy;

   3. If request is for a dose increase, request meets one of the following (a, b, or c):* a. As adjuvant therapy for breast cancer: New dose does not exceed 3.6 mg/kg every 21 days for a maximum of 14 doses; Page 2 of 6

   CLINICAL POLICY Ado-Trastuzumab Emtansine b. For all other indications: New dose does not exceed 3.6 mg/kg every 21 days; c. 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 – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

7. 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

8. 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 policy – 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 receptor 2 protein NSCLC: non-small cell lung cancer Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported
   • Boxed warning(s): hepatotoxicity, cardiac toxicity, and embryo-fetal toxicity Page 3 of 6

   CLINICAL POLICY Ado-Trastuzumab Emtansine V. Dosage and Administration
   Indication Dosing Regimen Breast cancer Adjuvant therapy for early breast cancer with residual disease
   3.6 mg/kg IV Q3WK (21-day cycle) for a total of 14 cycles unless there is disease recurrence or unmanageable toxicity. Maximum Dose 3.6 mg/kg Metastatic breast cancer 3.6 mg/kg IV Q3WK (21-day cycle) until disease progression or unmanageable toxicity. VI. Product Availability
   Single-use vial: 100 mg, 160 mg VII.