Abemaciclib (Verzenio) Form

Abemaciclib (Verzenio®) is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6).
FDA Approved Indication(s) Verzenio is indicated: • In combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. In combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. In combination with fulvestrant for the treatment of adult patients with HR-positive, HER2- negative advanced or metastatic breast cancer with disease progression following endocrine therapy. • • • As monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy 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 Verzenio 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 has both of the following characteristics (a and b): a. HR-positive (i.e., estrogen receptor (ER) and/or progesterone receptor (PR) positive); b. HER2-negative; Page 1 of 8

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   Abemaciclib

   5. Verzenio is prescribed in one of the following ways (a or b):
      a. For advanced, recurrent or metastatic disease, one of the following (i, ii, or iii): In combination with fulvestrant; i. ii. As a single agent after disease progression on an endocrine therapy and chemotherapy (e.g., docetaxel, gemcitabine) in the metastatic setting; iii. In combination with an aromatase inhibitor (e.g., letrozole, anastrozole, exemestane) as part of initial endocrine based therapy, and: 1) If male, an agent that suppresses testicular steroidogenesis (e.g., gonadotropin-releasing hormone agonists); b. For node-positive, early breast cancer with a high risk of recurrence, both (i and ii) of the following (see Appendix D): i. As adjuvant treatment; ii. In combination with endocrine therapy (tamoxifen or an aromatase inhibitor);

5. If prescribed as part of combination therapy and member is a premenopausal female, member has been treated with ovarian ablation or is receiving ovarian suppression (see Appendix D);

   7. Member has not previously experienced disease progression on a CDK 4/6 inhibitor therapy (e.g., Ibrance®, Kisqali®);
   8. Verzenio is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Ibrance, Kisqali);
   9. For brand name Verzenio requests, member must use generic abemaciclib, if available, unless contraindicated or clinically significant adverse effects are experienced;
   10. Request meets one of the following (a or b): a. Dose does not exceed one of the following (i or ii): i. For combination therapy: 300 mg per day (two 150 mg tablets per day);
       ii. For monotherapy: 400 mg per day (two 200 mg 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):
   11. 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 Page 2 of 8

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   Abemaciclib

   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.
      II. Continued Therapy A. Breast Cancer (must meet all):
   3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Verzenio for breast cancer and has received this medication for at least 30 days;
   4. Member is responding positively to therapy;
6. Dose is ≥ 100 mg per day;

7. Verzenio is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Ibrance, Kisqali);

   5. For brand name Verzenio requests, member must use generic abemaciclib, if available, unless contraindicated or clinically significant adverse effects are experienced;
   6. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed one of the following (i or ii): i. For combination therapy: 300 mg per day (two 150 mg tablets per day);
      ii. For monotherapy: 400 mg per day (two 200 mg tablets per day); b. New dose is supported by practice guideline 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
      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.
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   Abemaciclib 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 CDK: cyclin-dependent kinase ER: estrogen receptor FDA: Food and Drug Administration
   HER2: human epidermal growth factor receptor 2 HR: hormone receptor NCCN: National Comprehensive Cancer Network PR: progesterone receptor 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 1 mg PO QD
   25 mg PO QD
   60 mg PO QD 500 mg IM into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter 2.5 mg PO QD 20 to 40 mg PO QD 40 mg PO QID Endocrine Therapy anastrozole (Arimidex®)
   exemestane (Aromasin®) Fareston® (toremifene) Faslodex® (fulvestrant) letrozole (Femara®) tamoxifen (Nolvadex®, Soltamox®) megestrol acetate Chemotherapy
   capecitabine (Xeloda®) Various carboplatin (Paraplatin®) Various cisplatin (Platinol-AQ®) Various Various cyclophosphamide (Cytoxan®) docetaxel (Taxotere®) doxorubicin (Lipodox®, Doxil®, Adriamycin®) epirubicin (Ellence®) gemcitabine (Gemzar®) Halaven® (eribulin) Various Various Various Various Various 1 mg/day 25 mg/day 60 mg/day 500 mg/day 2.5 mg/day 40 mg/day 160 mg/day Varies Varies Varies Varies Varies Varies Varies Varies Varies Page 4 of 8

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   Abemaciclib Drug Name Dosing Regimen Ixempra® (ixabepilone) paclitaxel (Abraxane®, Taxol®) vinorelbine (Navelbine®) Various Various Various Dose Limit/ Maximum Dose Varies Varies Varies Drug names 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 None reported Appendix D: General Information • High risk breast cancer is defined by the NCCN as those with ≥ 4 positive lymph nodes (confirmed preoperatively and/or at surgery), or 1–3 positive lymph nodes with one or both of the following: histologic grade 3 disease, tumor size ≥ 5 cm (on pre-operative imaging and/or at surgery. • NCCN recommendations in breast cancer: o The NCCN recommends that men with breast cancer be treated similarly to postmenopausal women, except that the use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis. o The NCCN supports use of Verzenio in premenopausal women when used concomitantly with an aromatase inhibitor or fulvestrant. Along with this combination therapy, patients should also be treated with ovarian ablation/suppression. Ovarian ablation can be achieved with surgical oophorectomy or ovarian irradiation. Ovarian suppression can be achieved with luteinizing hormone-releasing hormone agonists (e.g., goserelin, leuprolide). o Although the FDA labeled indication limits combination use with fulvestrant to second line, the NCCN recommends this combination as both first and second line (category 1). • For disease progression while on a CDK4/6 inhibitor, there is no data to support retreatment with another CDK4/6 inhibitor-containing regimen.
   • Fluoxymesterone and ethinyl estradiol for breast cancer are other endocrine therapies, but they are no longer commercially available. V. Dosage and Administration
   Indication Breast cancer
   Dosing Regimen In combination with fulvestrant, tamoxifen, or an aromatase inhibitor: 150 mg PO BID Maximum Dose Combination therapy: 300 mg/day Monotherapy: 400 mg/day As monotherapy: 200 mg PO BID
   If a dose reduction to < 100 mg/day is required, therapy should be discontinued. VI. Product Availability
   Tablets: 50 mg, 100 mg, 150 mg, 200 mg Page 5 of 8

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   Abemaciclib VII.