Overview

This document addresses the use of Faslodex (fulvestrant). Faslodex is an estrogen receptor (ER) antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells. The FDA approved indications for Faslodex include

• Monotherapy
  • Advanced breast cancer, hormone receptor (HR)-positive (+) disease, in postmenopausal women with disease progression following endocrine therapy
  • Advanced breast cancer, HR +, human epidermal growth factor receptor 2 (HER2)-negative (-) disease, in postmenopausal women not previously treated with endocrine therapy
• Combination therapy
  • Advanced or metastatic breast cancer, HR+, HER2-negative disease, in postmenopausal women in combination with ribociclib (Kisqali), as initial endocrine based therapy or following disease progression on endocrine therapy
  • Advanced or metastatic breast cancer, HR+, HER2-negative disease, in combination with palbociclib (Ibrance) or abemaciclib (Verzenio) in women with disease progression after endocrine therapy.

Slamon and colleagues (2018) reported results from the MONALEESA-3 study (NCT02422615), a phase III, double-blind, placebo-controlled international study of participants with HR+/HER2- advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in advanced setting. The primary endpoint was progression free survival (PFS). In this phase III trial postmenopausal women and men were randomized (2:1) to receive ribociclib in combination with fulvestrant (n=484) or placebo plus fulvestrant (n=242). Data suggests efficacy of ribociclib in combination with fulvestrant; median PFS was improved with the addition of ribociclib to fulvestrant versus placebo plus fulvestrant arm (20.5 versus 12.8 months, respectively; HR 0.59, 95% CI 0.480-0.732; P<0.001). Benefits were consistent across participants with and without prior endocrine treatment. Authors concluded that "the efficacy results seen here for treatment-naïve advanced disease as well as those from other studies of CDK4/6 inhibitors in HR-positive/HER2-negative breast cancer support the study of ribociclib in early HR-positive/HER2-negative disease."

New agent Piqray (alpelisib)

is FDA approved for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR) positive, human epithelial growth factor receptor 2 (HER2) negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. At the time of this review, the National Comprehensive Cancer Network (NCCN) had yet to update their breast cancer guidelines to include the approval of Piqray.

Other Uses

The National Comprehensive Cancer Network® (NCCN) provides additional recommendations with a category 2A level of evidence for Faslodex in breast cancer with or without trastuzumab for systemic therapy for ER and/or PR- positive recurrent stage IV disease in postmenopausal women and recurrent, metastatic, low-grade serous ovarian cancer, or high-risk uterine cancer disease. NCCN provides additional category 2A level of evidence for Faslodex in ovarian cancer in low-grade serous carcinoma if an aromatase inhibitor was previously given. The guidelines discussion section for this use does not provide any supporting data and the treatment algorithm for primary systemic therapy regimens provides a 2B level rating for hormonal therapy in low-grade serous carcinoma.

Also NCCN provides additional recommendations with a category 2A level of evidence for Faslodex in urothelial cancer, hormonal therapy for low-grade Endometrial Stromal Sarcoma (ESS) or Hormone receptor-positive uLMS (Uterine leiomyosarcoma).

In addition NCCN provides a category 2A level of evidence for Faslodex in grade 1 or 2 endometrial histological carcinomas, in those with small tumor volume or and indolent growth pace. At this time there is no published evidence of safety and efficacy to support any of these off-label indications.

Definitions and Measures

Metastasis:

The spread of cancer from one part of the body to another; a metastatic tumor contains cells that are like those in the original (primary) tumor and have spread.

Relapse or recurrence:

After a period of improvement, during which time a disease (for example, cancer) could not be detected, the return of signs and symptoms of illness or disease. For cancer, it may come back to the same place as the original (primary) tumor or to another place in the body.

Clinical Criteria

When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose.

Faslodex (fulvestrant)

Requests for Faslodex (fulvestrant) may be approved if the following criteria are met:

1. Individual has a diagnosis of recurrent or metastatic breast cancer, hormone receptor (HR)-positive; AND
2. Individual is using as monotherapy (along with ovarian suppression if indicated) or in combination with CDK4/6 inhibitor; OR
3. Individual is using in combination with a CDK4/6 inhibitor or Piqray (alpelisib).

Requests for Faslodex (fulvestrant) may not be approved when the above criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

• J9395 Injection, fulvestrant, 25 mg [Faslodex]
• J9393 Injection, fulvestrant [Teva]
• J9394 Injection, fulvestrant [Fresenius Kabi]

ICD-10 Diagnosis

• C50.011-C50.929 Malignant neoplasm of breast
• C79.81 Secondary malignant neoplasm of breast
• Z17.0 Estrogen receptor positive status [ER+]
• Z85.3 Personal history of malignant neoplasm of breast

Document History

Reviewed: 02/24/2023