Description

Fam-trastuzumab deruxtecan-nxki (Enhertu®) is a human epidermal growth factor-2 (HER2)-directed antibody and topoisomerase inhibitor conjugate. Once bound to the HER2 receptor on tumor cells, fam-trastuzumab deruxtecan (Enhertu) undergoes internalization and cleavage of the tetrapeptide-based linker by lysosomal enzymes. Once released from the antibody-drug conjugate, deruxtecan causes DNA damage and apoptosis.

Criteria

Coverage is subject to the specific terms of the member’s benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

The use of fam-trastuzumab deruxtecan (Enhertu) may be considered medically when the presence of the HER2-overexpression is confirmed by the following:

HER2-overexpression must be verified by ANY ONE of the following FDA approved diagnostic tests:

• An immunohistochemical (IHC) assay with a result of 3+ (positive); or
• A positive fluorescence in situ hybridization (FISH) test (ratio greater than 2.0); or
• Single-probe in situ hybridization (ISH) test with average HER2 copy number 6.0 signals/cell or greater; or
• Dual-probe ISH test HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater; or HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater.

Confirmatory tests should be performed for borderline results as follows:

• If IHC assay has a result of 2+, confirm with ISH test of the same sample or a new test with IHC or ISH (if new sample available); or
• If FISH test has a HER2 gene/chromosome 17 ratio of 1.8-2.0, confirm with FISH re-test; additional cell counting and recalculation of the ratio; or IHC assay; or
• If single-probe ISH assay has an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available); or
• If dual-probe ISH assay has a HER2/CEP17 ratio less than 2.0 and an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

Food and Drug Administration (FDA) Indications:

The use of fam-trastuzumab deruxtecan (Enhertu) may be considered medically necessary in individuals 18 years of age and older when ALL of the following criteria are met:

• Diagnosis of HER2-positive unresectable or metastatic breast cancer; and
• The individual has had two (2) or more prior anti-HER2-based regimens in the metastatic setting.

The use of fam-trastuzumab deruxtecan (Enhertu) for any other indication than listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

National Comprehensive Cancer Network (NCCN) Recommendations:

The use of fam-trastuzumab deruxtecan (Enhertu) may be considered medically necessary in individuals 18 years of age and older for the following:

• As single-agent therapy for recurrent or stage IV (M1) HER2-positive disease, following two or more lines of prior HER2-targeted therapy that is either of the following:
  • Hormone receptor-negative; or
  • Hormone receptor-positive.

The use of fam-trastuzumab deruxtecan (Enhertu) for any other indication than listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Note: Do not substitute fam-trastuzumab deruxtecan-nxki (Enhertu) for or with trastuzumab (Herceptin), trastuzumab biosimilars, or ado-trastuzumab emtansine (Kadcyla).

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Diagnosis Codes

Professional Statements and Societal Positions Guidelines

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