CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Enhertu (fam-trastuzumab deruxtecan‑nxki) — Coverage Criteria

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.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyEnhertu (fam-trastuzumab deruxtecan‑nxki) — Coverage Criteria

Policy CodePolicy N/A

Change TypeMinor / no material changes

Effective DateJun 30, 202615d

Next Review DateJun 30, 202615d

Key ActionSubmit prior authorization with documented HER2 status (IHC/ISH) and requested dosing; typical approvals are for 12 months when criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthstypical authorization length

5.4 mg/kg q3wcommon dosing

6.4 mg/kg q3wselect indications dosing

HER2 IHC/ISHbiomarker required

Tennessee citedstate statute

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

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:

FDA indications: 1) HER2-positive metastatic/unresectable breast cancer for patients who have received a prior anti‑HER2 regimen in the metastatic, neoadjuvant, or adjuvant setting and developed recurrence during or within 6 months of completing therapy (Enhertu as monotherapy). 2) First‑line treatment of unresectable/metastatic HER2‑positive breast cancer in combination with pertuzumab. 3) HER2‑mutant unresectable or metastatic non‑small cell lung cancer (mutation‑driven indication). 4) HER2‑positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma after prior trastuzumab‑based regimen. 5) HER2‑positive unresectable/metastatic solid tumors when appropriate prior systemic therapy has been given and there is no satisfactory alternative; other FDA‑listed indications as specified in the product labeling.

Based on FDA indications in the product labeling.

Compendial and Other Solid Tumor Uses

Covered compendial uses when all listed conditions are met:

Compendial uses: Specific HER2‑positive or HER2‑amplified tumors listed in recognized compendia (including, but not limited to: recurrent HER2‑positive breast cancer; NSCLC with HER2 mutations; HER2‑low and HER2‑ultralow breast cancer; HER2‑positive esophageal, gastric or gastroesophageal junction cancer; and other HER2‑positive solid tumors such as colorectal, cervical, endometrial, ovarian, vaginal, vulvar, ampullary, salivary gland, pancreatic, small bowel, occult primary, appendiceal, bladder, biliary tract tumors) may be covered when diagnostic documentation and prior‑treatment requirements are met; all other indications are considered experimental/investigational and not medically necessary.

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:

Breast cancer (HER2‑positive): Requested medication will be used as a single agent for disease that had no response to preoperative systemic therapy, or for recurrent, metastatic, or unresectable disease; OR will be used in combination with pertuzumab as first‑line treatment for unresectable or metastatic disease; OR will be used as adjuvant therapy for residual high‑risk disease following neoadjuvant therapy.

Authorization of 12 months may be granted.

Breast cancer (HER2‑low): Member has HER2‑low (IHC 1+ or IHC 2+/ISH‑) disease that had no response to preoperative systemic therapy, or is recurrent, metastatic, or unresectable; requested medication will be used as a single agent.

Authorization of 12 months may be granted.

Breast cancer (HER2‑ultralow): Member has HER2‑ultralow (IHC 0 with membrane staining) recurrent, metastatic, or unresectable disease AND either hormone receptor positive with visceral crisis or endocrine therapy refractory, or hormone receptor negative; requested medication will be used as a single agent.

Specified dosing regimens

Medication quantity limits and dosing regimens specified in the document

Enhertu dosing: Intravenous 5.4 mg/kg every 3 weeks5.4 mg/kg q3w

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

Medication (product-level) and dosingNDC | mixed

Enhertu (fam-trastuzumab deruxtecan-nxki)

Product referenced with indication-specific dosing limits

Dose and frequency

Standard dosing5.4 mg/kg IV every 3 weeks (applied to most indicated diagnoses)

Select-indication dosing6.4 mg/kg IV every 3 weeks for select indications (e.g., esophageal/gastric/GEJ adenocarcinoma; salivary gland tumor)

Administration routeIntravenous infusion every 3 weeks

Quantity limits sourceMedication quantity limits listed per diagnosis in the policy (see diagnosis-specific entries)

Provider Requirements and Authorization Process

Prior Authorization

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)

Documentation Required

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

Denial Risk

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

Denial Risk

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

Documentation Required

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

Documentation Required

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

HER2-positive / HER2-low / HER2-ultralow definitions

HER2-positiveIHC 3+ or ISH positive (IHC 3+ or ISH +).

HER2-lowIHC 1+ or IHC 2+ with ISH negative (IHC 1+ or IHC 2+/ISH-).

HER2-ultralowIHC 0 with membrane staining as determined by an FDA‑approved test.

Off-label use

Off-label use definitionUse of an FDA‑approved drug for an indication not listed in the FDA‑approved labeling.

Tennessee coverage requirementOff‑label coverage requires recognition in a statutorily recognized reference compendium or published peer‑reviewed medical literature per TCA §56‑7‑2352.

Policy consequenceOff‑label indications not recognized in compendia/literature may be excluded from mandated coverage consideration and may be denied.

Line of Therapy

first-line | subsequent

line: Enhertu is indicated for later‑line settings for patients who have received prior systemic therapy for metastatic/unresectable disease; for selected indications (e.g., first‑line HER2‑positive breast cancer) it may be used in combination with pertuzumab as first‑line therapy.

Biomarker and Mutation Requirements

HER2 (IHC, ISH) and HER2 (ERBB2) mutations

HER2-positive biomarker requirementTumor IHC 3+ or ISH positive required to document HER2‑positive status for applicable indications.

HER2-low / ultralow biomarker requirementHER2‑low (IHC 1+ or IHC 2+/ISH-) and HER2‑ultralow (IHC 0 with membrane staining) must be determined by an FDA‑approved test and documented for breast cancer indications.

HER2 (ERBB2) mutation requirement for NSCLCActivating HER2 (ERBB2) mutation detected by an FDA‑approved test is required for the NSCLC mutation‑specific indication.

Documentation for prior authorizationSubmit HER2 status (IHC score, ISH result) and hormone receptor (HR) status as part of prior authorization documentation.

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

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyEnhertu (fam-trastuzumab deruxtecan‑nxki) — Coverage Criteria

Policy CodePolicy N/A

Change TypeMinor / no material changes

Effective DateJun 30, 202615d

Next Review DateJun 30, 202615d

Key ActionSubmit prior authorization with documented HER2 status (IHC/ISH) and requested dosing; typical approvals are for 12 months when criteria are met.

SourceLink

On This Page

Authorization of 12 months may be granted.

Non‑small cell lung cancer (NSCLC): Requested medication will be used as a single agent for recurrent, advanced, metastatic, or unresectable disease AND the member has an activating HER2 (ERBB2) mutation or HER2 overexpression (IHC 3+) AND the member has not experienced disease progression on a prior HER2‑targeted agent (e.g., ado‑trastuzumab emtansine [Kadycla]).

Authorization of 12 months may be granted.

Esophageal/Gastric/GEJ adenocarcinoma: Member has HER2‑positive disease and is not a surgical candidate or requires subsequent treatment for unresectable locally advanced, recurrent, or metastatic disease; requested medication will be used as a single agent.

Authorization of 12 months may be granted.

Solid tumors (general): Tumor is HER2‑positive (IHC 3+ or 2+), disease is unresectable, metastatic, advanced, recurrent, or persistent, member received prior systemic treatment with no satisfactory alternative treatment options, and requested medication will be used as a single agent.

Authorization of 12 months may be granted.