ZOLADEX, Goserelin Acetate Form

Goserelin acetate (Zoladex®) is a gonadotropin-releasing hormone (GnRH) receptor agonist. FDA Approved Indication(s) Zoladex 3.6 and 10.8 are indicated for the treatment of prostatic carcinoma: • In combination with flutamide for the management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma. Treatment should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy • As palliative treatment of advanced carcinoma Zoladex 3.6 is indicated: • For the management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy
• As an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding
• For the palliative treatment of advanced breast cancer in pre- and perimenopausal women Limitation(s) of use: Experience with Zoladex for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months. 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 Zoladex is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Prostate Cancer (must meet all):

1. Diagnosis of prostate cancer;
2. Prescribed by or in consultation with an oncologist or urologist;
3. Age ≥ 18 years;

4. Request meets one of the following (a or b): a. Dose does not exceed 3.6 mg per month and/or 10.8 mg per 3 months; 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 Page 1 of 10

   CLINICAL POLICY Goserelin Acetate Approval duration: 12 months B. Breast Cancer (must meet all):

5. Diagnosis of breast cancer;
6. Request is for Zoladex 3.6 mg;
7. Prescribed by or in consultation with an oncologist;
8. Age ≥ 18 years;
9. Request meets one of the following (a or b): a. Dose does not exceed 3.6 mg per month; 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: 12 months C. Endometriosis (must meet all):
10. Diagnosis of endometriosis;
11. Request is for Zoladex 3.6 mg;
12. Prescribed by or in consultation with a gynecologist;
13. Age ≥ 18 years;
14. Endometriosis as a cause of pain is one of the following (a or b): a. Surgically confirmed;
    b. Both of the following (i and ii): i. Clinically suspected; ii. Failure of a 3-month trial of one of the following within the last year, unless clinically adverse effects are experienced or all are contraindicated (1, 2, or 3): 1) A nonsteroidal anti-inflammatory drug (see Appendix B for examples); 2) An oral or injectable depot contraceptive (see Appendix B for examples); 3) A progestin (see Appendix B for examples);
    6. For members currently receiving treatment with goserelin, total duration of therapy has not exceeded 6 months;
    7. Dose does not exceed 3.6 mg per month. Approval duration: 6 months D. Dysfunctional Uterine Bleeding (must meet all):
15. Diagnosis of dysfunctional uterine bleeding;
16. Request is for Zoladex 3.6 mg;
17. Prescribed by or in consultation with a gynecologist;
18. Age ≥ 18 years;
19. Prescribed as an endometrial-thinning agent prior to endometrial ablation;

20. For members currently receiving treatment with goserelin, member has not yet received two implants;

    7. Dose does not exceed 3.6 mg per month. Approval duration: 8 weeks (2 implants per ablation procedure) Page 2 of 10

    CLINICAL POLICY Goserelin Acetate E. Gender Dysphoria, Gender Transition (off-label) (must meet all):

21. Diagnosis of gender dysphoria or request is for gender transition;
22. Prescribed by or in consultation with both of the following (a and b): a. An endocrinologist; b. A provider with expertise in gender dysphoria and transgender medicine based on a certified training program or affiliation with local transgender health services (e.g., mental health professional such as psychologist, psychiatrist, see Appendix D);
    3. Age and pubertal development - meets one of the following (a or b): a. Member is < 18 years of age and has reached or passed through Tanner Stage 2; ___ Age ranges approximating Tanner Stage 2 pubertal development extend from 8 to 13 years of age in girls and 9 to 14 years of age in boys. b. Member is ≥ 18 years of age and has failed to achieve physiologic hormone levels with gender-affirming hormonal therapy (e.g., estrogen, testosterone) unless contraindicated or clinically significant adverse effects are experienced;
23. Member demonstrates understanding of expected GnRH analogue treatment outcomes and has given consent for such treatment;
    5. If member has a psychiatric comorbidity, member is followed by mental health provider;
    6. Psychosocial support will be provided during treatment;
24. Dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
    Approval duration: 12 months
    F. Other diagnoses/indications (must meet 1 or 2):
    1. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

25. 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. Prostate Cancer (must meet all):

    1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zoladex for prostate cancer and has received this medication for at least 30 days; Page 3 of 10

    CLINICAL POLICY Goserelin Acetate

    2. Member is responding positively to therapy;
26. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 3.6 mg per month and/or 10.8 mg per 3 months; 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: 12 months B. Breast Cancer (must meet all):
    1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Zoladex for breast cancer and has received this medication for at least 30 days;
27. Request is for Zoladex 3.6 mg;
28. Member is responding positively to therapy;
29. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 3.6 mg per month; 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: 12 months C. Endometriosis (must meet all):
    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Request is for Zoladex 3.6 mg;
30. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: improvement in dysmenorrhea, dyspareunia, pelvic pain/induration/tenderness, size of endometrial lesions;
    4. Total duration of goserelin therapy has not exceeded 6 months;
31. If request is for a dose increase, new dose does not exceed 3.6 mg per month. Approval duration: up to a total treatment duration of 6 months D. Dysfunctional Uterine Bleeding (must meet all):
32. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Request is for Zoladex 3.6 mg;

33. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: improvement in Page 4 of 10

    CLINICAL POLICY Goserelin Acetate dysmenorrhea, dyspareunia, pelvic pain/induration/tenderness, size of endometrial lesions;

    4. Member has not yet received two implants;
34. If request is for a dose increase, new dose does not exceed 3.6 mg per month. Approval duration: 4 weeks (2 implants total per ablation procedure) E. Gender Dysphoria, Gender Transition (off-label) (must meet all):
    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Member is responding positively to therapy (e.g., member continues to meet their individual goals of therapy for gender dysphoria);
    3. If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
       Approval duration: 12 months
       F. Other diagnoses/indications (must meet 1 or 2):
    4. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

35. 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: 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 – 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 FDA: Food and Drug Administration GnRH: gonadotropin-releasing hormone
    Page 5 of 10

    CLINICAL POLICY Goserelin Acetate NCCN: National Comprehensive Cancer WPATH: World Professional Association Network for Transgender Health 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 NSAIDs: ibuprofen, naproxen, fenoprofen, ketoprofen, mefenamic acid, meclofenamate, indomethacin, tolmetin, diclofenac, etodolac, diflunisal, meloxicam, piroxicam Combined oral estrogen-progesterone contraceptives: ethinyl estradiol + (desogestrel, ethynodiol diacetate, drospirenone, etonogestrel, levonorgestrel, norelgestromin, norethindrone, norgestimate, or norgestrel); estradiol valerate + dienogest; mestranol + norethindrone Progestin-only oral contraceptives: norethindrone Depot progestin contraceptive: medroxyprogesterone acetate Endometriosis Varies – refer to specific prescribing information Dose Limit/ Maximum Dose Varies – refer to specific prescribing information Endometriosis 1 tablet PO QD (may vary per specific prescribing information) 1 tablet per day (may vary per specific prescribing information) 0.35 mg PO QD See regimen Endometriosis 0.35 mg PO QD Endometriosis IM: 150 mg per 3 months (every 13 weeks) SC: 104 mg per 3 months (every 12-14 weeks) 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. *Examples provided may not be all-inclusive Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity; pregnancy unless used for treatment of advanced breast cancer • Boxed warning(s): None reported Appendix D: General Information • World Professional Association for Transgender Health (WPATH) offers their Global Education Institute (GEI) Certified Training Courses: Best Practices in Transgender Medical and Mental Health Care. Additionally, the following link provides a search tool to locate WPATH member providers: https://www.wpath.org/provider/search • Transgender Care Therapy Certification Training is also offered by the International Transgender Certification Association (ITCA). Professionals with expertise in Page 6 of 10

    CLINICAL POLICY Goserelin Acetate transgender care can be located using the following search tool: https://transgendercertification.com/locate-a-professional/ • The WPATH Standards of Care Version 8 recommend that adolescents are managed by a multidisciplinary care team that involves both medical and mental health professionals. The list of key disciplines includes but is not limited to: adolescent medicine/primary care, endocrinology, psychology, psychiatry, speech/language pathology, fertility, social work, support staff, and the surgical team. The need to include a healthcare professional with some expertise in mental health does not dictate the inclusion of a psychologist, psychiatrist or social work in every assessment. Instead, a general practitioner, nurse or other qualified clinician could fulfill this requirement as long as they have sufficient expertise to diagnose gender incongruence, recognize mental health concerns, distinguish between these concerns and gender dysphoria, incongruence or diversity, assist a transgender person in care planning and preparing for gender affirmative medical and surgical treatments, and refer to a mental health professional if needed. V. Dosage and Administration
    Drug Name Indication Dosing Regimen Goserelin acetate (Zoladex 3.6, 10.8)
    Prostate cancer - stage B2-C
    3.6 mg SC 8 weeks before radiotherapy, followed by 10.8 mg SC in 28 days (alternative: 4 injections of 3.6 mg at 28-day intervals, 2 preceding and 2 during radiotherapy) 3.6 mg SC every 28 days Goserelin acetate (Zoladex 3.6)
    Prostate cancer - palliative therapy Endometriosis 3.6 mg SC every 28 days 3.6 mg SC every 28 days 3.6 mg SC every 28 days Dysfunctional uterine bleeding Breast cancer

    • palliative therapy Maximum Dose See regimen 3.6 mg per 28 days 3.6 mg per 28 days (6 months total treatment) 3.6 mg per 28 days (2 doses total per ablation procedure) 3.6 mg per 28 days VI. Product Availability
      Implant: 3.6 mg, 10.8 mg VII.