​

Last Review Date: 03/05/2024

Date of Origin: 01/01/2012

Dates Reviewed: 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 09/2017, 11/2017, 02/2018, 05/2018, 09/2018, 12/2018, 03/2019, 04/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 03/2021, 03/2022, 03/2023, 12/2023, 03/2024

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• 250 mg/5 mL single-dose prefilled syringe: 6 syringes first 29 days initially (loading doses), then 2 syringes per 28 days thereafter as maintenance

2. Max Units (per dose and over time) [HCPCS Unit]:

Ovarian Cancer

• Loading Dosing: 20 billable units on day 1 and 10 billable units on days 15 and 29
• Maintenance Dosing: 10 billable units every 28 days

Endometrial Cancer

• 10 billable units every 28 days

Breast Cancer/Uterine Sarcoma

• Loading Dosing: 20 billable units every 14 days for 3 doses
• Maintenance Dosing: 20 billable units every 28 days

3. Initial Approval Criteria ^1-3

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Breast Cancer †‡ ^{1-3,4,7,10-13,16,17}

• Patient is postmenopausal, premenopausal with ovarian ablation/suppression, or male (sex assigned at birth); AND
  • Patient has advanced, metastatic, or recurrent unresectable invasive disease; AND
    • Patient has hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease with no visceral crisis; AND
      • • • • Used as initial therapy; AND
      • Used as a single agent; OR
      • Used in combination with a CDK 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib); OR
      • Used in combination with a non-steroidal aromatase inhibitor (i.e., anastrozole or letrozole) ¥ ‡; OR

• • • • • • Used as subsequent therapy; AND
  • Used as a single agent; OR
  • Used in combination with a non-steroidal aromatase inhibitor (i.e., anastrozole or letrozole) ¥ ‡; OR
  • Used in combination with a CDK 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) if a CDK 4/6 inhibitor was not previously used; OR
  • Used in combination with everolimus ‡; OR
  • Used in combination with alpelisib in patients who have PIK3CA activating mutation positive disease as determined by an FDA-approved or CLIA-compliant testv ‡; OR
  • Used in combination with capivasertib in patients with PIK3CA or AKT1 activating mutations or PTEN loss of function alterations, as determined by an FDA-approved or CLIA-compliant testv; AND

• Used for disease that has progressed on at least one endocrine-based regimen in the metastatic setting; OR
• Used for disease recurrence on or within 12 months of completing adjuvant therapy; OR
• Used after disease progression or recurrence after one or more prior lines of endocrine therapy (ET), including one line containing a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib); OR
• Patient has HR-positive, HER2-positive* disease as determined by an FDA-approved or CLIA-compliant testv‡; AND
  • • • Used as a single agent or in combination with trastuzumab; OR
• Patient has recurrent unresectable or metastatic inflammatory disease ‡; AND
  • Patient has HR-positive, HER2-negative disease with no visceral crisis; AND
    • • • Used as first line therapy; AND
          • Used as a single agent; OR
          • Used in combination with a non-steroidal aromatase inhibitor (i.e., anastrozole or letrozole) ¥; OR

• • • • • Used in combination with a CDK 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) if disease progression on adjuvant ET or with early disease relapse within 12 months of adjuvant ET completion; OR
      • Used as subsequent therapy; AND
        • Used as a single agent; OR
        • Used in combination with a non-steroidal aromatase inhibitor (i.e., anastrozole or letrozole) ¥; OR
        • Used in combination with everolimus; OR
        • Used in combination with a CDK 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) if a CDK 4/6 inhibitor was not previously used; OR
        • Used in combination with alpelisib in patients who have PIK3CA activating mutation positive disease as determined by an FDA-approved or CLIA-compliant testv; OR
        • Used in combination with capivasertib in patients with PIK3CA or AKT1 activating mutations or PTEN loss of function alterations, as determined by an FDA-approved or CLIA-compliant testv; AND
  • Used after disease progression or recurrence after one or more prior lines of ET, including one line containing a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib); OR
  • Patient has HR-positive, HER2-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
    • • • Used as a single agent or in combination with trastuzumab

¥ When an aromatase inhibitor is used in males, suppression of testicular steroidogenesis with a gonadotropin releasing hormone (GnRH) analog is required.

Ovarian Cancer (Epithelial, Fallopian Tube, or Primary Peritoneal Cancer) ‡ ^4,9,14

• Used as single agent therapy; AND
• Patient has recurrent low-grade serous carcinoma; AND
• Patient has previously received treatment with an aromatase inhibitor (i.e., letrozole, anastrozole, exemestane)

Endometrial Carcinoma (Uterine Neoplasms) ‡ ^4,8,15

• Used as single agent therapy; AND

• Patient has grade 1 or 2 endometrioid adenocarcinoma histology; AND
  • • • • Used in patients with a small tumor volume or an indolent growth pace; AND
        • Used as ONE of the following:

• • • • • Adjuvant treatment for stage IV disease; OR
        • Treatment for disseminated metastases or locoregional recurrence; OR

• • • • • Primary treatment in patients with locoregional extrauterine disease that is not suitable for primary surgery; OR
        • Primary treatment in patients with distant metastatic disease

Uterine Sarcoma (Uterine Neoplasms) ‡ ^4,15

• Used as single agent therapy; AND
  • • • • Used in patients with a small tumor volume or an indolent growth pace; AND
• Used for low-grade endometrial stromal sarcoma (ESS), adenosarcoma without sarcomatous overgrowth, or ER/PR positive uterine sarcoma; AND
  • Used following total hysterectomy for stage II-IV disease; OR
  • Used for metastatic or recurrent disease; OR
  • Used as primary treatment; AND
    • Disease is not suitable for primary surgery (disease is not amenable to resection or patient is not suitable for surgery based on comorbidities); OR
    • Patient has extrauterine disease diagnosed by biopsy or myomectomy

v If confirmed using an immunotherapy assay-http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-3

Coverage can be renewed based upon the following criteria:

• Patient continues to meet the indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND

• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: bleeding abnormalities, severe injection site reactions (including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy), etc.

5. Dosage/Administration ^1-3,8,9,17

6. Billing Code/Availability Information

HCPCS Code(s):

• J9395 – Injection, fulvestrant, 25 mg; 1 billable unit = 25 mg
• J9393 – Injection, fulvestrant (teva) not therapeutically equivalent to J9395, 25 mg; 1 billable unit = 25 mg
• J9394 – Injection, fulvestrant (fresenius kabi) not therapeutically equivalent to J9395, 25 mg; 1 billable unit = 25 mg

NDC(s):

• Faslodex 250 mg/5 mL single-dose prefilled syringe: 00310-0720-xx*
• Fulvestrant 250 mg/5 mL single-dose prefilled syringe (Teva): 00591-5019-xx Ψ
• Fulvestrant 250 mg/5 mL single-dose prefilled syringe (Fresenius Kabi): 63323-0715-xx Ψ

7. References

1. Faslodex [package insert]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; January 2021. Accessed February 2024.
2. Fulvestrant [package insert]. North Wales, PA; Teva Pharmaceuticals USA; November 2021. Accessed February 2024.
3. Fulvestrant [package insert]. Lake Zurich, IL; Fresenius Kabi; September 2021. Accessed February 2024.
4. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for fulvestrant. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed February 2024.
5. Chia S, Gradishar W, Mauriac L, et al. Double-blind, randomized placebo-controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone-receptor positive, advanced breast cancer: results from EFECT. J Clin Oncol 2008; 26:1664-1670.
6. Mauriac L, Romieu G, Bines J. Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial. Breast Cancer Res Treat 2009; 117:69-75.
7. Di Leo A, Jerusalem G, Petruzelka L, et al. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol 2010; 28:4594-4600.
8. Covens AL, Filiaci V, Gersell D. Phase II study of fulvestrant in recurrent/metastatic endometrial carcinoma: a Gynecologic Oncology Group study.  Gynecol Oncol. 2011 Feb;120(2):185-8. doi: 10.1016/j.ygyno.2010.10.015. Epub 2010 Nov 13.
9. Argenta PA, Thomas SG, Judson PL, et al. A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer. Gynecol Oncol. 2009 May;113(2):205-209.
10. Robertson JFR, Bondarenko IM, Trishkina E, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016;388(10063):2997‐3005. doi:10.1016/S0140-6736(16)32389-3.
11. Robertson JF, Osborne CK, Howell A, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials. Cancer. 2003;98(2):229‐238. doi:10.1002/cncr.11468.
12. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial [published correction appears in Lancet Oncol. 2016 Apr;17 (4):e136] [published correction appears in Lancet Oncol. 2016 Jul;17 (7):e270]. Lancet Oncol. 2016;17(4):425‐439. doi:10.1016/S1470-2045(15)00613-0.
13. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol. 2017;35(25):2875‐2884. doi:10.1200/JCO.2017.73.7585.
14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer Version 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed February 2024.
15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Uterine Neoplasms Version 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed February 2024.
16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer, Version 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed February 2024.
17. Turner NC, Oliveira M, Howell SJ, et al; CAPItello-291 Study Group. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023 Jun 1;388(22):2058-2070. doi: 10.1056/NEJMoa2214131.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A

​