Rucaparib (Rubraca) Form

Rucaparib (Rubraca®) is a poly (ADP-ribose) polymerase (PARP) inhibitor.
FDA Approved Indication(s) Rubraca is indicated: Ovarian cancer • For the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Prostate cancer • For the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 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 Rubraca is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Ovarian Cancer (must meet all):

1. Diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For brand Rubraca requests, member must use generic rucaparib, if available, unless contraindicated or clinically significant adverse events are experienced;

2. Prescribed as a single agent;

   6. Member meets one of the following (a or b):* a. Both i and ii (see Appendix F): i. Documentation of deleterious or suspected deleterious BRCA mutation; Page 1 of 9

   CLINICAL POLICY Rucaparib ii. Completed platinum-based chemotherapy and is in a complete or partial response; b. Both i and ii: i. Newly diagnosed stage II-IV disease (see Appendix D); ii. Completed first-line platinum-based chemotherapy regimen and is in a complete or partial response; *Prior authorization may be required

3. Member has not previously received a PARP inhibitor (e.g., Lynparza®, Talzenna®, Zejula®) (see Appendix D);
4. Request meets one of the following (a or b): a. Dose does not exceed any of the following (i or ii): i. 1,200 mg per day; ii. 4 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. Prostate Cancer (must meet all):
5. Diagnosis of metastatic CRPC as evidenced by disease progression despite androgen deprivation therapy (ADT) (see Appendix D);
6. Prescribed by or in consultation with an oncologist or urologist;
   3. Age ≥ 18 years;
   4. Documented deleterious germline and/or somatic BRCA mutation;
   5. For Rubraca requests, member must use generic rucaparib, if available, unless contraindicated or clinically significant adverse events are experienced;
7. Prescribed concurrently with systemic ADT (see Appendix D) or member has had a bilateral orchiectomy;
8. Failure of both of the following, unless clinically significant adverse effects are experienced or all are contraindicated (a and b): a. A taxane-based regimen (e.g., docetaxel);Prior authorization may be required for taxanes
   b. An androgen receptor-directed therapy (e.g. abiraterone, enzalutamide); *Prior authorization may be required for androgen receptor-directed therapies
9. Member has not previously received a PARP inhibitor (e.g., Lynparza, Talzenna, Zejula) (see Appendix D);

10. Request meets one of the following (a or b): a. Dose does not exceed any of the following (i or ii): i. 1,200 mg per day; ii. 4 capsules 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 Page 2 of 9

    CLINICAL POLICY Rucaparib Commercial – 12 months or duration of request, whichever is less C. 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
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, 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):
13. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Rubraca for a covered indication and has received this medication for at least 30 days;
14. For ovarian cancer: If request is for use in an adult member with a deleterious BRCA mutation who has been treated with two or more chemotherapies, provider attestation of acknowledgement for withdrawal for this indication due to risk of detrimental effect on overall survival (OS) in patients who used Rubraca (see Appendix E);
    3. For ovarian cancer: If request is for maintenance use in an adult member with non- deleterious BRCA mutation who is in a complete or partial response to platinum- based chemotherapy, provider attestation of acknowledgement for possible OS detriment with Rubraca use in this population (see Appendix F);

15. Member is responding positively to therapy;

    5. For Rubraca requests, member must use generic rucaparib, if available, unless contraindicated or clinically significant adverse events 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 any of the following (i or ii): i. 1,200 mg per day; ii. 4 tablets per day; b. 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 Page 3 of 9

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

16. 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

17. 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.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ADT: androgen deprivation therapy
    BRCA: breast cancer susceptibility gene CRPC: castration resistant prostate cancer FDA: Food and Drug Administration GnRH: gonadotropin-releasing hormone
    LHRH: luteinizing hormone-releasing hormone NCCN: National Comprehensive Cancer Network PARP: poly (ADP-ribose) polymerase 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 and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose Varies Ovarian Cancer: examples of chemotherapy agents Alimta® (pemetrexed) Alkeran® (melphalan) Avastin® (bevacizumab)
    carboplatin (Paraplatin®) cisplatin (Platinol-AQ®) cyclophosphamide (Cytoxan®) docetaxel (Taxotere®) Varies Page 4 of 9

    CLINICAL POLICY Rucaparib Drug Name Dosing Regimen Dose Limit/ Maximum Dose doxorubicin (Doxil®, Adriamycin®) etoposide (Vepesid®) gemcitabine (Gemzar®) ifosfamide (Ifex®) irinotecan (Camptosar®) oxaliplatin (Eloxatin®) topotecan (Hycamtin®) Hexalen® (altretamine) paclitaxel
    Prostate Cancer docetaxel abiraterone (Zytiga®, Yonsa®) Zytiga: 1,000 mg PO BID in combination with prednisone Yonsa: 500 mg PO QD in combination with methylprednisolone 160 mg PO QD
    enzalutamide (Xtandi®) 75 mg/m2 IV for 6 cycles Varies 1,000 mg QD; 1,000 mg BID if taking a strong CYP3A4 inducer Yonsa: 500 mg QD; 500 mg BID if taking a strong CYP3A4 inducer 160 mg/day; 240 mg/day if taking a strong CYP3A4 inducer Therapeutic alternatives 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
    • 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 (ADT) should be continued in the setting of CRPC while additional therapies are applied. • Examples of ADT include: o Bilateral orchiectomy (surgical castration) o Luteinizing hormone-releasing hormone (LHRH; also known as GnRH) 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, nilutamide (Nilandron®), Xtandi® (enzalutamide), Erleada® (apalutamide) o LHRH antagonist: Firmagon® (degarelix), Orgovyx® (relugolix) • There are 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 Page 5 of 9

    CLINICAL POLICY Rucaparib explicit recommendations in this regard (other than for ovarian cancer, where it states data is limited), and there are no randomized controlled trials evaluating such use.
    Appendix E: Withdrawal of Third-Line BRCA-Mutated Ovarian Cancer Indication • Clovis Oncology, manufacturer of Rubraca, voluntarily withdrew Rubraca for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. The withdrawal became effective as of June 10, 2022. • The decision was made in consultation with the FDA and based on ARIEL4 results showing a detrimental effect in terms of OS that was observed for rucaparib compared to the chemotherapy-containing control arm.
    • As OS detriment, for patients randomized to Rubraca, was observed at the final analysis of OS (70% of deaths reported). In the intention-to-treat population, median OS was 19.5 months in the Rubraca group compared to 25.4 months in the chemotherapy group, resulting in a HR of 1.31 (95% CI: 1.00, 1.73; p= 0.0507).
    • Physicians should not initiate new treatment with rucaparib for adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Appendix F: Restricted Ovarian Cancer Second-Line Setting Indication to BRCA-Mutated Population
    • The restriction to the BRCA-mutated population was based on the ARIEL3 final OS data that was submitted to the FDA by Clovis Oncology. Results showed patients without BRCA mutations with or without homologous recombination deficiency positive status had an increased risk of death with Rubraca (28% and 15%, respectively). The FDA requested that Clovis Oncology voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment to BRCA-mutated patients only.
    V. Dosage and Administration
    Indication Ovarian cancer Metastatic CRPC Dosing Regimen 600 mg PO BID. 600 mg PO BID. Patients receiving Rubraca should also receive a GnRH analog concurrently or should have had bilateral orchiectomy Maximum Dose 1,200 mg/day 1,200 mg/day VI. Product Availability
    Tablets: 200 mg, 250 mg, 300 mg VII.