Apalutamide (Erleada) Form

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

1. Diagnosis of prostate cancer that is characterized as one of the following (a or b): a. Non-metastatic and both of the following (i and ii): i. Castration-resistant, as evidenced by disease progression despite bilateral orchiectomy or other androgen deprivation therapy (see Appendix D); ii. Prostate-specific antigen doubling time (PSADT) ≤ 10 months; b. Metastatic and castration-sensitive;
2. Prescribed by or in consultation with an oncologist or urologist;
   3. Age ≥ 18 years;
   4. Member will use a gonadotropin-releasing hormone (GnRH) analog concurrently or has had a bilateral orchiectomy;
3. For brand Erleada requests, member must use generic apalutamide, if available, unless contraindicated or clinically significant adverse effects are experienced;

4. Request meets one of the following (a or b): a. Dose does not exceed 240 mg per day; b. 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: HIM – 12 months Commercial – 12 months or duration of request, whichever is less Page 1 of 5

   CLINICAL POLICY Apalutamide B. Other diagnoses/indications (must meet 1 or 2):

5. 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 and HIM.PA.33 for health insurance marketplace; 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 and HIM.PA.103 for health insurance marketplace; or
6. 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 and HIM.PA.154 for health insurance marketplace.
   II. Continued Therapy A. Prostate Cancer (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Erleada for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   3. If CRPC, there is no evidence of metastases;
   4. Member continues to use a gonadotropin-releasing hormone (GnRH) analog concurrently or has had a bilateral orchiectomy;
9. For brand Erleada requests, member must use generic apalutamide, if available, unless contraindicated or clinically significant adverse effects are experienced;
10. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 240 mg 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: HIM – 12 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 and HIM.PA.33 for health insurance marketplace; or Page 2 of 5

    CLINICAL POLICY Apalutamide 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 and HIM.PA.103 for health insurance marketplace; or

12. 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 and HIM.PA.154 for health insurance marketplace. 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 and HIM.PA.154 for health insurance marketplace or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration CRPC: castration-resistant prostate cancer CSPC: castration-sensitive prostate cancer GnRH: gonadotropin-releasing hormone Appendix B: Therapeutic Alternatives Not applicable Appendix C: Contraindications/Boxed Warnings None reported LHRH: luteinizing-hormone releasing- hormone PSADT: prostate-specific antigen doubling time 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, androgen deprivation therapy should be continued in the setting of CRPC while additional therapies are applied. • Examples of androgen deprivation therapy include: o Bilateral orchiectomy (surgical castration): o Luteinizing-hormone releasing-hormone (LHRH) agonist given with or without an anti-androgen:  LHRH agonists: Zoladex® (goserelin), leuprolide (Lupron Depot® or Eligard®), Trelstar® (triptorelin)  Anti-androgens: bicalutamide (Casodex®), flutamide (Eulexin®), nilutamide (Nilandron®), Xtandi® (enzalutamide), Erleada® (apalutamide), Nubeqa® (darolutamide) o LHRH antagonist: Firmagon® (degarelix), Orgovyx™ (relugolix) Page 3 of 5

    CLINICAL POLICY Apalutamide V. Dosage and Administration
    Indication Non-metastatic CRPC, metastatic CSPC Dosing Regimen 240 mg PO QD Maximum Dose 240 mg/day VI. Product Availability
    Tablets: 60 mg, 240 mg VII.