Enhertu (fam-trastuzumab deruxtecan‑nxki) — Coverage Criteria
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This policy governs prior authorization, coverage criteria, and quantity limits for Enhertu (fam-trastuzumab deruxtecan-nxki) for Blue Cross Blue Shield - Tennessee members for specified HER2-related oncologic indications.
No material clinical or coverage changes in this revision.
Coverage Criteria for Enhertu (fam-trastuzumab deruxtecan-nxki)
FDA-Approved Indications
Covered when ANY of the following FDA-approved indications are met and approval criteria are satisfied:
Based on FDA indications in the product labeling.
Compendial and Other Solid Tumor Uses
Covered compendial uses when all listed conditions are met:
Coverage limited to compendial list and when documentation/prior therapy requirements are satisfied.
Indication-specific authorization criteria
Authorization may be granted for 12 months when ALL of the following are met for the specified disease group:
Authorization of 12 months may be granted.
Authorization of 12 months may be granted.
Authorization of 12 months may be granted.
Authorization of 12 months may be granted.
Authorization of 12 months may be granted.
Authorization of 12 months may be granted.
Specified dosing regimens
Medication quantity limits and dosing regimens specified in the document
Applied to listed diagnoses including bowel adenocarcinoma, solid tumors, vaginal cancer, and vulvar cancer
All indications not specifically listed in the policy’s enumerated FDA-approved indications or the compendial uses list are considered experimental/investigational and therefore not medically necessary.
Off-label indications that are not recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature may be excluded from mandated coverage consideration in accordance with Tennessee Code Annotated Section 56-7-2352.
Uses of Enhertu that fall outside the enumerated FDA-approved indications and the compendial uses listed in this policy are considered not medically necessary because they are experimental/investigational and may be denied.
Product and Dosing Coding
| Enhertu (fam-trastuzumab deruxtecan-nxki) | Product referenced with indication-specific dosing limits |
Provider Requirements and Authorization Process
Prior Authorization Required
Prior authorization is required. Typical approvals are for up to 12 months when coverage criteria are met. Prior authorization requests must specify the dosing regimen consistent with the medication quantity limits (generally IV 5.4 mg/kg every 3 weeks for most indications; select indications per formulary may specify 6.4 mg/kg q3w).
- Authorization length: up to 12 months when criteria met
- Dosing: IV 5.4 mg/kg every 3 weeks for most diagnoses; IV 6.4 mg/kg every 3 weeks where specifically noted (see medication quantity limits)
Required Diagnostic Documentation
Submit documentation of HER2 status (e.g., IHC score, ISH testing) and hormone receptor (HR) status as part of the prior authorization request. Also include relevant diagnostic and treatment history, prior systemic therapies, and rationale for use.
- Required tests: HER2 IHC and/or ISH results
- Hormone receptor status (ER/PR)
- Prior treatment history and rationale
Other Indications Not Covered (Investigational)
All indications not specifically listed in the policy's covered indications (including the compendial uses list) are considered experimental/investigational and are not medically necessary. Providers should not submit requests for uses outside the listed indications unless supported by a statutorily recognized compendium or peer-reviewed literature.
- Unlisted uses are investigational and not eligible for coverage
- Exceptions: off-label uses recognized in standard compendia or peer-reviewed literature per Tennessee mandate
Off-Label Coverage Limitation
Off-label uses will be considered only when the use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature in accordance with Tennessee Code Annotated §56-7-2352. Off-label requests lacking such recognition may be denied.
- Coverage of off-label uses requires recognition in a statutorily recognized compendium or peer-reviewed literature
- Non-recognized off-label uses may be denied
Prior HER2‑Targeted Therapy Consideration
Prior HER2‑targeted therapy status must be documented for certain indications. For NSCLC, the member must not have experienced disease progression on a prior HER2‑targeted drug (for example, ado‑trastuzumab emtansine [Kadycla]).
- NSCLC-specific requirement: no disease progression on prior HER2-targeted therapy (e.g., Kadycla)
Step Therapy
No formal step therapy requirements are specified in this section. Providers should consult referenced compendia and the policy clinical criteria for recommended sequencing of therapies and appropriate prior treatments.
- No step therapy required per this section
- Refer to NCCN and other compendia for regimen sequencing
Supporting Documentation
Supporting documentation to include with the authorization request: pathology reports with HER2 testing (IHC and/or ISH), hormone receptor status, prior systemic therapy records, treatment response documentation, and any relevant compendia citations or peer‑reviewed literature supporting off‑label uses.
- Pathology reports with HER2 IHC/ISH results
- Hormone receptor (ER/PR) status
- Records of prior systemic therapies and treatment response
- Citations from NCCN, Drugdex, AHFS, or Enhertu package insert as applicable
Background
Enhertu (fam-trastuzumab deruxtecan-nxki) is an antibody-drug conjugate indicated for multiple HER2-expressing or HER2-mutant malignancies, including HER2-positive and HER2-low breast cancer, HER2-mutant non-small cell lung cancer, HER2-positive gastric/gastroesophageal junction adenocarcinoma, and selected HER2-positive solid tumors. Coverage under this policy is tied to documented HER2 status and the indication-specific prior-treatment criteria and dosing regimens described in the policy.
Definitions and Biomarker Criteria
Line of Therapy
first-line | subsequent
Biomarker and Mutation Requirements
Covered Regimens and Dosing
| Indication / Tumor Type | Her2 Requirement / Prior Therapy | Regimen | Coverage Status |
|---|---|---|---|
| Ampullary adenocarcinoma | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Biliary tract cancer | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Bladder cancer | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Breast cancer (HER2-positive / HER2-low / HER2-ultralow) | |||
| HER2 status documented (IHC/ISH) and prior therapy per indication-specific criteria | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Cervical cancer | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Colorectal cancer (including appendiceal and anal adenocarcinoma) | |||
| HER2-amplified / positive per compendia and prior therapy required | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Endometrial carcinoma | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Esophageal, gastric, gastroesophageal junction (GEJ) adenocarcinoma | |||
| HER2-positive and prior trastuzumab-based regimen as specified | |||
| Intravenous 6.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Non-small cell lung cancer (HER2-mutant) | |||
| Confirmed HER2 (ERBB2) activating mutation or IHC 3+ per criteria; no progression on prior HER2-targeted drug for mutation-specific setting | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Occult primary | |||
| HER2-positive per policy and prior therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Ovarian, fallopian tube, primary peritoneal cancer | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Pancreatic adenocarcinoma | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Salivary gland tumor | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 6.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Small bowel adenocarcinoma | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Bowel adenocarcinoma | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Solid tumors (other HER2-positive solid tumors) | |||
| Tumor HER2-positive (IHC 3+ or ISH+) and prior systemic treatment with no satisfactory alternative | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Vaginal cancer | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met | |||
| Vulvar cancer | |||
| Documented HER2-positive per policy and prior systemic therapy as specified | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Covered when criteria met |
| Indication / Tumor Type | Regimen (route, dose, frequency) | Notes | Coverage Status |
|---|---|---|---|
| Ampullary adenocarcinoma | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Biliary tract cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Bladder cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Breast cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Applies to HER2-positive, HER2-low, and HER2-ultralow indications per criteria | |||
| covered | |||
| Cervical cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Colorectal cancer (including appendiceal and anal) | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Endometrial carcinoma | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Esophageal/gastric/GEJ adenocarcinoma | |||
| Intravenous 6.4 mg/kg every 3 weeks | |||
| Policy specifies 6.4 mg/kg q3w for this diagnosis | |||
| covered | |||
| NSCLC (HER2-mutant) | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Applies when HER2 mutation or IHC 3+ overexpression is documented | |||
| covered | |||
| Occult primary | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Ovarian / fallopian / primary peritoneal cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Pancreatic adenocarcinoma | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Salivary gland tumor | |||
| Intravenous 6.4 mg/kg every 3 weeks | |||
| Policy specifies 6.4 mg/kg q3w for this diagnosis | |||
| covered | |||
| Small bowel / bowel adenocarcinoma | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Solid tumors (other HER2-positive) | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Applies to listed solid tumors such as vaginal, vulvar; per policy | |||
| covered | |||
| Vaginal cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered | |||
| Vulvar cancer | |||
| Intravenous 5.4 mg/kg every 3 weeks | |||
| Maximum dosing regimen per policy | |||
| covered |
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