TALZENNA, Talazoparib Tosylate Form

Talazoparib (Talzenna™) is a poly (ADP-ribose) polymerase (PARP) inhibitor. FDA Approved Indication(s) Talzenna is indicated for the treatment of adult patients with
• Deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, as a single agent. Select patients for therapy based on an FDA-approved companion diagnostic for Talzenna. • Homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), in combination with enzalutamide. 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 Talzenna is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Diagnosis of recurrent, locally advanced, or metastatic breast cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For brand Talzenna requests, member must use generic talazoparib, if available, unless contraindicated or clinically significant adverse effects are experienced;
2. Prescribed as a single agent;
   6. Documentation of HER2-negative disease;
   7. Mutations in the BRCA genes;
   8. Member has not previously received a PARP inhibitor (e.g., Lynparza®, Rubraca®, Zejula®);

3. Request meets one of the following (a or b):* a. Dose does not exceed any of the following (i or ii): i. 1 mg per day; ii. 1 capsule per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
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   CLINICAL POLICY Talazoparib *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. Prostate cancer (must meet all):

4. Diagnosis of metastatic CRPC, as evidenced by disease progression despite bilateral orchiectomy or other androgen deprivation therapy (ADT) (see Appendix D);
5. Prescribed by or in consultation with an oncologist or urologist;
   3. Age ≥ 18 years;
   4. For brand Talzenna requests, member must use generic talazoparib, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. Documentation of a HRR gene mutation;
   6. Prescribed concurrently with Xtandi®;
   7. Member will use a gonadotropin-releasing hormone (GnRH) analog concurrently or has had a bilateral orchiectomy (see Appendix D);
7. Member has not previously received a PARP inhibitor (e.g., Lynparza®, Rubraca®, Zejula®);
8. Request meets one of the following (a or b): a. Dose does not exceed any of the following (i or ii): i. 0.5 mg per day; ii. 1 capsule 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 C. Other diagnoses/indications (must meet 1 or 2):
9. 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

10. 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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    CLINICAL POLICY Talazoparib II. Continued Therapy A. All Indications in Section I (must meet all):

11. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Talzenna for a covered indication and has received this medication for at least 30 days;
12. Member is responding positively to therapy;
    
    3. For brand Talzenna requests, member must use generic talazoparib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    4. If request is for a dose increase, request meets one of the following (a, b, or c): a. For breast cancer: New dose does not exceed both of the following (i and ii): i. 1 mg per day; ii. 1 capsule per day; b. For mCRPC: New dose does not exceed both of the following (i and ii): i. 0.5 mg per day; ii. 1 capsule per day; 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 – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
13. 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

14. 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 Talazoparib IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ADP: adenosine diphosphate ADT: androgen deprivation therapy BRCA: breast cancer gene gBRCAm: mutations in the germline BRCA genes
    FDA: Food and Drug Administration GnRH: gonadotropin-releasing hormone HER2: human epidermal growth factor receptor 2
    Appendix B; Therapeutic Alternatives Not applicable HR: hormone receptor HRR: homologous recombination repair mCRPC: metastatic castration-resistant prostate cancer NCCN: National Comprehensive Cancer Network
    PARP: poly (ADP-ribose) polymerase Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information
    • The FDA approved indication for talazoparib includes using the diagnostic tool BRACAnalysis CDx™ by Myriad Genetic Laboratories. It is available at http://www.fda.gov/companiondiagnostics. • There is insufficient data regarding the use of consecutive PARP inhibitors. Most PARP inhibitor pivotal trials excluded prior PARP inhibitor use, the NCCN does not make any explicit recommendations (other than for ovarian cancer, where they state data is limited), and there are no randomized controlled trials evaluating such use. • NCCN recommended use: Single agent therapy (preferred regimen) for patients with no response to preoperative systemic therapy, or recurrent unresectable (local or regional) or stage IV (M1) human epidermal growth factor receptor 2 (HER2)-negative, BRCA 1/2- germline mutated disease that is: o Hormone receptor-negative o Hormone receptor-positive o Hormone receptor-positive with visceral crisis or endocrine therapy refractory
    • Examples of ADT include: o Bilateral orchiectomy (surgical castration) o Luteinizing hormone-releasing hormone (LHRH) given with or without an anti- androgen  LHRH (or GnRH) agonists: Zoladex® (goserelin), Supprelin® (histrelin), leuprolide (Lupron Depot®, Eligard®), and Trelstar® (triptorelin)  Anti-androgens: bicalutamide (Casodex®), flutamide, nilutamide (Nilandron®) o LHRH antagonist: Firmagon® (degarelix), Orgovyx™ (relugolix) V. Dosage and Administration
    Indication Breast cancer Dosing Regimen 1 mg PO QD Maximum Dose 1 mg/day Page 4 of 7

    CLINICAL POLICY Talazoparib Indication Dosing Regimen For patients with moderate renal impairment (CrCl 30 – 59 mL/min): 0.75 mg PO QD Maximum Dose For patients with severe renal impairment (CrCl 15 – 29 mL/min): 0.5 mg PO QD 0.5 mg PO QD in combination with enzalutamide 0.5 mg/day mCRPC For patients with moderate renal impairment (CrCl 30 – 59 mL/min): 0.35 mg PO QD For patients with severe renal impairment (CrCl 15 – 29 mL/min): 0.25 mg PO QD VI. Product Availability
    Capsules: 0.1 mg, 0.25 mg, 0.35 mg, 0.5 mg, 0.75 mg, 1 mg VII.