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; and
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).
The use of fam-trastuzumab deruxtecan (Enhertu) may be considered medically necessary in individuals 18 years of age and older when the following criteria are met:
Breast Cancer
- Diagnosis of HER2-positive or HER2-low unresectable or metastatic breast cancer; and
- The individual has received a prior anti-HER2-based regimen in the metastatic setting; or
- The individual has had disease recurrence during or within six (6) months of completing neoadjuvant or adjuvant therapy; or
Gastric or Gastroesophageal Junction Adenocarcinoma
- Diagnosis of locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma; and
- The individual has received a prior trastuzumab-based regimen; or
Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
- Diagnosis of unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations; and
- The individual has received prior systemic based therapy; or
Compendia Sources
Fam-trastuzumab deruxtecan (Enhertu) may be considered medically necessary for treatment of any of the current category 1 or 2A NCCN recommendations.
The use of fam-trastuzumab deruxtecan (Enhertu) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.
Procedure Codes
