The safety and efficacy of Faslodex as combination therapy with Palbociclib were tested in an international, randomized, double-blind, parallel group, multicenter study. Faslodex plus palbociclib was compared to Faslodex plus placebo conducted in women with HR-positive, HER2-negative advanced breast cancer, regardless of their menopausal status, whose disease progressed on or after prior endocrine therapy. A total of 521 pre/postmenopausal women were randomized 2:1 to Faslodex plus palbociclib or Faslodex plus placebo. Consistent results were observed across patient subgroups
of disease site, sensitivity to prior hormonal therapy and menopausal status. Confirmed overall response rate in patients with measurable disease as assessed by the investigator was 24.6% in the Faslodex plus palbociclib and was 10.9% in the Faslodex plus placebo arm. Duration of response was 9.3 months in the Faslodex plus palbociclib arm compared with 7.6 months in the Faslodex plus placebo arm. At the time of final analysis of PFS, OS data were not mature with 29% of events.

The safety and efficacy of Falsodex was studied against anastrozole 1 mg in the FALCON trial, an innternational randomized, double-blind trial. Patients either received faslodex 500 mg IM injection on days 0, 14, 28, and then every 28 days following or anastrazole 1 mg tablet once daily. Patients enrolled were postmenopausal with oestrogen receptor-positive or progresterone receptor-positive, or both, and were locally advanced or metastatic. Patients had a ECOG score of 0-2 and at least one measurable or non-measurable lesion. There were 524 patients who were enrolled in the trial and 462 were randomized. The primary endpoint of this trial was progression free survival, determined by the response evaluation criteria in solid tumors. Progression free survival (PFS) was longer in the Faslodex group (HR 0.797 [0.637-0.999], P=0.0486), with a median PFS of 16.6months versus 13.8 months. The most common adverse events were arthralgia (17% vs. 10%) and hot flashes (11% vs. 10%). 7% of the Faslodex group and 5% of the anastrazole group discontinued due to adverse events.

The most common side effects observed in patients treated with Faslodex are (>5% incidence) include injection site pain, headache, back pain, fatigue, pain in extremities, asthenia, hot flash, nausea/vomiting, constipation, bone pain, and cough. Additional safety concerns include an increased risk of bleeding and fetal harm in pregnant women.

In March 2019 the generic formulation of Faslodex (fulvestrant) was FDA approved.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

1. Faslodex (fulvestrant) is medically necessary for the following FDA-approved indications:

a. HR-positive advanced breast cancer in post-menopausal women with disease progression following endocrine therapy
b. HR-positive, HER-2 negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy
c. HR-positive, HER-2 negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy
d. HR-positive, HER-2 negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib, as initial endocrine based therapy or following disease progression on endocrine therapy
[INFORMATIONAL NOTE: Treatment with endocrine therapy ]includes third generation aromatase inhibitors (anastrazole, letrozole,or exemestane) or tamoxifen]

a. 500 mg intramuscularly into the buttocks as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter

Max units (per dose and over time) – 1 billable unit = 25 mg
· Breast cancer
o Loading dosing: 20 units every 14 days for 3 doses
o Maintenance dosing: 20 units every 28 days

[INFORMATIONAL NOTE: As per the FDA approved package insert, Faslodex is administered by a healthcare professional. A dose of 250 mg is recommended in patients with moderate hepatic impairment to be administered intramuscularly into the buttock as one 5 mL injection on Days 1, 15, 29 and once monthly thereafter.]

A. Breast Cancer
• Therapy for recurrent or stage IV (M1) hormone receptor-positive disease in postmenopausal women (Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis) or for premenopausal women treated with ovarian ablation/suppression
  • as first-line or second-line therapy and beyond as a single agent for human epidermal growth factor receptor 2 (HER2)-negative disease with no visceral crisis (preferred regimen)
  • as first-line therapy in combination with a non-steroidal aromatase inhibitor (anastrozole or letrozole) for HER2-negative disease with no visceral crisis (preferred regimen)
  • as first-line therapy in combination with a CDK 4/6 inhibitor (abemaciclib, palbociclib or ribociclib) for HER2-negative disease with no visceral crisis (all preferred regimens)
  • as second-line therapy and beyond in combination with everolimus for HER2-negative disease with no visceral crisis (preferred regimen)
  • as a second-line therapy and beyond in combination with a CDK4/6 inhibitor (abemaciclib, palbociclib or ribociclib) for HER-2 negative disease with no visceral crisis if a CDK4/6 inhibitor was not previously used (preferred regimen)
  • as second-line therapy and beyond in combination with alpelisib for HER2-negative disease with no visceral crisis if PIK3CA mutation positive (preferred regimen)
  • as a single agent for HER2-positive disease
  • in combination with trastuzumab for HER2-positive disease
B. Uterine Neoplasms - Endometrial Carcinoma
• Adjuvant treatment for surgically staged patients as preferred single-agent hormone therapy typically used for grade 1 or 2 endometrioid histologies, preferably in patients with small tumor volume or an indolent growth pace
  • with or without EBRT and with or without vaginal brachytherapy for stage III-IV disease
• · Primary treatment as preferred single-agent hormone therapy typically used for grade 1 or 2 endometrioid histologies, preferably in patients with small tumor volume or an indolent growth pace
  • may be considered for select patients with disease limited to the uterus that is not suitable for primary surgery
  • with sequential external beam radiation therapy (EBRT) and brachytherapy for disease that is not suitable for primary surgery in patients with suspected or gross cervical involvement
  • with sequential EBRT and with or without brachytherapy for locoregional extrauterine disease that is not suitable for primary surgery
  • with or without EBRT and/or stereotactic body radiation therapy for distant metastases that are suitable for primary surgery
  • for distant metastases that are not suitable for primary surgery
• Preferred single-agent hormone therapy typically used for grade 1 or 2 endometrioid histologies, preferably in patients with small tumor volume or an indolent growth pace
  • for disseminated metastases (hormone therapy is preferred as initial therapy for asymptomatic or ER/PR positive disseminated metastases)
  • with sequential external beam radiation therapy (EBRT) for local/regional recurrence in patients with disease in pelvic, para-aortic or common iliac lymph nodes
  • with or without sequential tumor-directed EBRT for local-regional recurrence in patients with microscopic residual upper abdominal or peritoneal disease
  • with or without sequential palliative EBRT or brachytherapy for local/regional recurrence in patients who have received prior EBRT to site of recurrence
C. Uterine Neoplasms - Uterine Sarcoma
• Therapy for low-grade ESS or estrogen receptor/progesterone receptor positive (ER/PR+) uLMS preferably in patients with small tumor volume or an indolent growth pace
  • for disease that is not suitable for primary surgery
  • following total hysterectomy with bilateral salpingo-oophorectomy for stage II-IV low-grade ESS
  • consider following total hysterectomy with or without bilateral salpingo-oophorectomy (TH ± BSO) for stage II-IV III ER/PR+ uLMS
  • following TH ± BSO for stage IV ER/PR+ uLMS
  • consider postoperatively for resectable isolated metastases
  • for unresectable isolated metastases or disseminated disease
  • for a radiologically isolated vaginal/pelvic recurrence
D. Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer
• Useful in certain circumstances for disease persistence or recurrence of low-grade serous carcinoma
  • for progression on primary, maintenance, or recurrence therapy
  • for stable or persistent disease (if not on maintenance therapy)
  • for complete remission and relapse <6 months after completing chemotherapy
  • for radiographic and/or clinical relapse in patients with previous complete remission and relapse after ≥6 months after completing prior chemotherapy

There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy. See generally, Local Coverage Article: Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents (A53049). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Fulvestrant (Faslodex)
Faslodex (Fulvestrant)

References:
1. Faslodex^® [package insert]. AstraZeneca Pharmaceuticals. Wilmington, DE. November 2019.

2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 3.2020; National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed March 29, 2020.

3. Ellis M, et al. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study. J Clin Oncol. 2015 Nov 10;33(32):3781-7. doi: 10.1200/JCO.2015.61.5831. Epub 2015 Sep 14.

4. Cristofanilli M. 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. Lancet Oncol. 2016 Mar 2. pii: S1470-2045(15)00613-0. doi: 10.1016/S1470-2045(15)00613-0.

5. Fulvestrant. National Comprehensive Cancer Network: Drugs and Biologics Compendium. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix. aspx?AID=90. Accessed 3/28/20

6. ClinicalTrials.gov accessed March 2020 at https://clinicaltrials.gov/ct2/results?term= fulvestrant=Search

7. Robertson JFR, et. All. Fulvestrant 500 mg versus anastrozole 1 mg for hormone-receptor positive advanced breast cancer (FALCON): an international, randomized, double-blind, phase 3 trial. Lancet. 2016: 388 (10063). 2997-3005.

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