Overview

This document addresses the use of Margenza (margetuximab-cmkb) injection. Margenza is a HER2/neu receptor antagonist FDA approved, in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Clinical criteria

Breast cancer is a type of tumor comprised of malignant (cancerous) cells that start to grow in the breast and may spread (metastasize) to surrounding tissues and other areas of the body (American Cancer Society, 2016). Breast cancer is commonly treated by various modalities which include combinations of surgery, radiation therapy, chemotherapy and hormone therapy (National Cancer Institute, 2019). The prognosis and selection of therapies can be affected by clinical and pathologic features of the tumor. One of these includes the human epidermal growth factor receptor 2 gene ERBB2 which is commonly referred to as HER2. Other names for this gene include NEU, Her-2, HER-2/neu and c-erb B2. Initially the HER2 gene was detected in frozen breast tumor samples. Amplification of the HER2 gene was later correlated to overexpression of protein levels in samples of breast cancer.

Approximately 276,000 patients are diagnosed with invasive breast cancer each year, with approximately one in five cases being classified as HER-2 positive.

Margenza

Margenza may lead to reductions in left ventricular ejection fraction. Exposure to Margenza during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

National Comprehensive Cancer Network (NCCN)

The National Comprehensive Cancer Network (NCCN) provides additional recommendations with a category 2A level of evidence for the use of Margenza in invasive and inflammatory breast cancer as third-line therapy and beyond in combination with chemotherapy for HER2-positive disease.

SOPHIA Trial Update

There is an update to the SOPHIA trial (Rugo et. al. 2021) for final overall survival (OS) results looking at margetuximab versus trastuzumab in those with previously treated with HER2 positive advance breast cancer. The abstract at this time states Margetuximab safety was comparable with trastuzumab; however, final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab (Rugo et. al. 2022).

Definitions and Measures

HER2 testing (adapted from American Society of Clinical Oncology/College of American Pathologists):

Positive HER2:

• IHC 3+ based on circumferential membrane staining that is complete, intense. (Observed in a homogeneous and contiguous population and within > 10% of the invasive tumor cells).
• ISH positive based on:
1. Single-probe average HER2 copy number ≥ 6.0 signals/cell*
2. Dual-probe HER2/CEP 17 ratio ≥ 2.0* with an average HER2 copy number ≥ 4.0 signals/cell
3. Dual-probe HER2/CEP17 ratio ≥ 2.0* with an average HER2 copy number < 4.0 signals/cell
4. Dual-probe HER2/CEP17 ratio < 2.0* with an average HER2 copy number ≥ 6.0 signals/cell

* (Observed in a homogeneous and contiguous population and within >10% of the invasive tumor cells. By counting at least 20 cells within the area)

Equivocal HER2:

• IHC 2+ based on circumferential membrane staining that is incomplete and/or weak/moderate and within >10% of the invasive tumor cells or complete and circumferential membrane staining that is intense and within ≤10% of the invasive tumor cells.

ISH Equivocal:

• Single-probe average HER2 copy number ≥ 4.0 and < 6.0 signals/cell
• Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number ≥ 4.0 signals/cell

Negative HER2:

• IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within > 10% of the invasive tumor cells
• IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells
• ISH negative based on:
  • Single-probe average HER2 copy number < 4.0 signals/cell
  • Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell

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.

Monoclonal antibody: A protein developed in the laboratory that can locate and bind to specific substances in the body and on the surface of cancer cells.

Progressive Disease (PD): Cancer that is growing, spreading, or getting worse.

Refractory Disease: Illness or disease that does not respond to treatment.

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.

Margenza (margetuximab-cmkb)

Requests for Margenza (margetuximab-cmkb) may be approved if the following criteria are met:

1. Individual has a diagnosis of metastatic HER2-positive (HER2+) breast cancer (NCCN 1) confirmed by one of the following:
   1. Immunohistochemistry (IHC) is 3 +; OR
   2. In situ hybridization (ISH) positive;
2. Individual has had at least two or more prior anti-HER2 therapies, and at least one in the metastatic setting (Label, NCCN 2A);
3. Individual is using in combination with chemotherapy, capecitabine, eribulin, gemcitabine, or vinorelbine (NCCN 2A; Rugo 2021).

Requests for Margenza (margetuximab-cmkb) 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

J9353

ICD-10 Diagnosis

• Injection, margetuximab-cmkb, 5 mg [Margenza]
• C50.011-C50.929 Malignant neoplasm of breast
• C79.81 Secondary malignant neoplasm of breast
• D05.00-D05.92 Lobular carcinoma in situ of breast
• Z85.3 Personal history of malignant neoplasm of breast
• Z17.0 Estrogen receptor positive status (ER+)

Document History

Revised: 02/24/2023