XTANDI, Enzalutamide Form

Enzalutamide (Xtandi®) is an androgen receptor inhibitor.
FDA Approved Indication(s) Xtandi is indicated for the treatment of patients with: • Castration-resistant prostate cancer (CRPC) • Metastatic castration-sensitive prostate cancer (CSPC) • Non-metastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis 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 Xtandi is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Prostate Cancer (must meet all):

1. Diagnosis of one of the following (a, b, or c): a. CRPC, as evidenced by disease progression despite bilateral orchiectomy or other androgen deprivation therapy (ADT) (see Appendix D);
   b. Metastatic CSPC; c. nmCSPC;
2. Prescribed by or in consultation with an oncologist or urologist;
   3. Age ≥ 18 years;
   4. For Xtandi requests, member must use generic enzalutamide, if available, unless contraindicated or clinically significant adverse effects are experienced;
   5. If request is for CRPC or metastatic CSPC, prescribed concurrently with a gonadotropin-releasing hormone (GnRH) analog or member has had a bilateral orchiectomy;
3. If prescribed concurrently with Talzenna®, request is for metastatic CRPC; Prior authorization may be required for Talzenna

4. If request is for nmCSPC, member has biochemical recurrence at high risk for metastasis as evidenced by both of the following (a and b): a. Prostate-specific antigen (PSA) doubling time ≤ 9 months; b. One of the following (i or ii): Page 1 of 7

   CLINICAL POLICY Enzalutamide i. PSA values ≥ 1 ng/mL if member had prior radical prostatectomy (with or without radiotherapy) as the primary treatment for prostate cancer; ii. PSA values ≥ 2 ng/mL above the nadir (lowest point) if member had prior radiotherapy only;

5. Request meets one of the following (a, b, c, or d): a. If prescribed concomitantly with a strong CYP2C8 inhibitor (e.g., gemfibrozil): Dose does not exceed both of the following (i and ii): i. 80 mg per day; ii. 2 capsules or 1 tablet per day; b. Dose does not exceed both of the following (i and ii): i. 160 mg per day; ii. 4 capsules or 2 tablets per day; c. If prescribed concomitantly with a strong CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital): Dose does not exceed both of the following (i and ii): i. 240 mg per day; ii. 6 capsules or 3 tablets per day; d. 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):
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.
   II. Continued Therapy A. Prostate Cancer (must meet all):
8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Xtandi for prostate cancer and has received this medication for at least 30 days;

9. Member is responding positively to therapy; Page 2 of 7

   CLINICAL POLICY Enzalutamide

10. For Xtandi requests, member must use generic enzalutamide, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. If request is for a dose increase, request meets one of the following (a, b, c, or d): a. If prescribed concomitantly with a strong CYP2C8 inhibitor (e.g., gemfibrozil): New dose does not exceed both of the following (i and ii): i. 80 mg per day; ii. 2 capsules or 1 tablet per day; b. New dose does not exceed both of the following (i and ii): i. 160 mg per day; ii. 4 capsules or 2 tablets per day; c. If prescribed concomitantly with a strong CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital): New dose does not exceed both of the following (i and ii): i. 240 mg per day; ii. 6 capsules or 3 tablets per day; d. 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):
12. 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

13. 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.
    Page 3 of 7

    CLINICAL POLICY Enzalutamide IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ADT: androgen deprivation therapy
    CRPC: castration-resistant prostate cancer CSPC: castration-sensitive prostate cancer FDA: Food and Drug Administration GnRH: gonadotropin-releasing hormone LHRH: luteinizing hormone-releasing hormone
    Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings None reported NCCN: National Comprehensive Cancer Network nmCSPC: non-metastatic castration- sensitive prostate cancer PSA: prostate-specific antigen Appendix D: General Information
    • CRPC is prostate cancer that progresses clinically, radiographically, or biochemically despite castrate levels of serum testosterone (< 50 ng/dL). Per the NCCN, ADT should be continued in the setting of CRPC while additional therapies are applied. o Examples of ADT include:  Bilateral orchiectomy (surgical castration)  Luteinizing hormone-releasing hormone (LHRH) agonist given with or without an anti-androgen: • LHRH agonists: Zoladex® (goserelin), Vantas® (histrelin), leuprolide (Lupron Depot®, Eligard®), and Trelstar® (triptorelin) • Anti-androgens: bicalutamide (Casodex®), flutamide (Eulexin®), nilutamide (Nilandron®), Xtandi® (enzalutamide), Erleada® (apalutamide)  LHRH antagonist: Firmagon® (degarelix), Orgovyx® (relugolix) V. Dosage and Administration
    Indication CRPC, metastatic CSPC, nmCSPC Dosing Regimen 160 mg (two 80 mg tablets) PO QD.
    Patients with CRPC or metastatic CSPC receiving Xtandi should also receive a GnRH analog concurrently or should have had bilateral orchiectomy. Patients with nmCSPC with high-risk biochemical recurrence may be treated with Xtandi with or without a GnRH analog. For patients who receive Xtandi with or without a GnRH analog, treatment can be suspended if PSA is undetectable (< 0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA has increased to ≥ 2.0 ng/mL for patients who had Maximum Dose 160 mg/day; 240 mg/day if taking a strong CYP3A4 inducer Page 4 of 7

    CLINICAL POLICY Enzalutamide Indication Dosing Regimen prior radical prostatectomy or ≥ 5.0 ng/mL for patients who had prior primary radiation therapy. Maximum Dose VI. Product Availability
    • Capsule: 40 mg • Tablets: 40 mg, 80 mg VII.