mhn Enhertu coverage update & Prior Auth

Coverage Criteria

Continuation Therapy

Continuation of therapy is covered when ALL of the following are met

Continuation Therapy - All Indications

Current treatment: Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Enhertu for a covered indication and has received this medication for at least 30 days30 days
Response: Member is responding positively to therapy
Dose change: If request is for a dose increase, new dose must meet one of: (a) for breast cancer, NSCLC, or IHC 3+ solid cancers: new dose does not exceed 5.4 mg/kg every 3 weeks; (b) for gastric/GEJ adenocarcinoma: new dose does not exceed 6.4 mg/kg every 3 weeks; (c) new dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Continuation / Dose Change Criteria

Covered when ALL of the following are met for any indication listed in Section I:

Continuing therapy and response: Member is currently receiving Enhertu via Centene benefit or documentation shows member has received Enhertu for at least 30 days; member is responding positively to therapy.30 days

From Section A items 1 and 2

Dose increase limits: If request is for a dose increase, new dose must meet one of: (a) for breast cancer, NSCLC, or IHC 3+ solid cancers: <=5.4 mg/kg q3w; (b) for gastric/GEJ adenocarcinoma: <=6.4 mg/kg q3w; (c) new dose supported by practice guidelines or peer-reviewed literature with prescriber submission of evidence.see text

Section A item 3

Regimen requirement: Prescribed regimen must be FDA-approved or recommended by NCCN.

Coverage groups (summary)

Policy updated to cover additional indications and provide exceptions per guideline alignment.

New or expanded indications: Includes use as adjuvant therapy in rectal cancer; IHC 3+ solid tumors; and off-label criteria for cervical cancer, salivary gland tumors, and endometrial carcinoma.

Details of specific clinical criteria are contained elsewhere in the full policy.

HER2-low breast cancer exception: For HR-positive HER2-low breast cancer, prior endocrine therapy requirement may be bypassed if the member has visceral crisis per NCCN guidance.

Applies only when visceral crisis is present.

If Enhertu has had a label change within the prior 6 months that is not yet reflected in this policy, providers should follow the applicable no‑coverage or non‑formulary policy for the relevant line of business. For drugs on the formulary or PDL, refer to the no coverage criteria policies (CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, CP.PMN.255 for Medicaid). For drugs not on the formulary or PDL, refer to the non‑formulary policies (CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, CP.PMN.16 for Medicaid).

Non‑FDA approved indications that are not addressed in this policy are excluded from coverage unless the prescriber supplies sufficient documentation of efficacy and safety per the applicable off‑label use policy. Refer to CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, or CP.PMN.53 for Medicaid for requirements to support off‑label use or evidence of coverage documentation.

When state Medicaid coverage provisions conflict with the terms of this clinical policy, the state Medicaid provisions take precedence. Providers should consult the applicable state Medicaid manual for the controlling coverage rules for Medicaid members.

Uses of Enhertu that are not FDA‑approved and are not supported by adequate off‑label evidence as defined in the referenced off‑label use policies are considered not authorized. Requests for such non‑FDA uses must include the documentation specified by the off‑label policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) to be considered for coverage.

Initial Therapy Criteria and Dosing

Initial authorization

Initial authorization requires meeting diagnosis-specific prior therapy, prescriber, age, and dosing criteria as specified below.

Prescriber requirement: Prescribed by or in consultation with an oncologist

Dose limit - initial: Initial dosing must meet one of: (a) for breast cancer, NSCLC, and IHC 3+ solid tumors: 5.4 mg/kg IV every 3 weeks (maximum 5.4 mg/kg); (b) for gastric/GEJ adenocarcinoma: 6.4 mg/kg IV every 3 weeks (maximum 6.4 mg/kg); (c) dose supported by practice guidelines or peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence).

Initial Therapy Dosing

Initial dosing per indication:

Breast/NSCLC/IHC 3+ tumors: Dose = 5.4 mg/kg IV every 3 weeks; maximum 5.4 mg/kg.

Continuation Therapy and Dose Change Criteria

Continuation criteria

Continuation requests require documentation of current use and positive response; dose increases are constrained by indication-specific maximums or literature support.

Documentation of current use: Provider must document current receipt of Enhertu via Centene benefit or provide clinical documentation that the member has received Enhertu for at least 30 days.

Clinical response: Member demonstrates positive response to therapy as documented in clinical records.

Continuation Therapy

Continuation criteria for members already on therapy:

Current therapy: Member currently receiving Enhertu via Centene benefit or documentation shows at least 30 days of therapy; member demonstrating positive response.

Step Therapy and Therapeutic Alternatives

Indication	Prior lines of therapy required before authorization
IHC 3+ solid tumors	Failure of ≥1 prior line of standard systemic regimen for the disease, or no available standard treatment as a satisfactory alternative
Breast cancer (HER2-positive)	Failure of one prior anti‑HER2‑based regimen unless contraindicated or clinically significant adverse effects; rapid progression within 6 months of neoadjuvant/adjuvant therapy (12 months if pertuzumab‑containing)
Breast cancer (HER2‑low)	Failure of ≥1 prior line of chemotherapy; if HR‑positive, prior endocrine therapy is expected unless ineligible or visceral crisis (see exception)
Gastric/GEJ adenocarcinoma	Failure of a trastuzumab‑based regimen
NSCLC with activating HER2 (ERBB2) mutations	Failure of one prior line of chemotherapy
Colon/Rectal cancer (off‑label)	Failure of or contraindication to ≥2 FDA‑approved medications for the diagnosis OR prescribed as adjuvant single‑agent for specified rectal cancer scenario (see criteria)
Other NCCN‑recommended off‑label uses (cervical, salivary gland, endometrial)	Typically single‑agent following failure of ≥1 prior therapy (specifics vary by tumor type per policy)

Therapeutic category / source	Examples of therapeutic alternatives that may be considered prior to approval
HER2‑positive breast cancer — NCCN systemic therapy examples	Aromatase inhibitor ± trastuzumab; aromatase inhibitor ± lapatinib; pertuzumab + trastuzumab + docetaxel; other systemic options (eribulin, capecitabine, gemcitabine, nab‑paclitaxel, paclitaxel)
HER2‑low / HR+ breast cancer — endocrine and systemic options	Endocrine therapies (tamoxifen, letrozole, anastrozole, exemestane) and systemic agents (CDK4/6 inhibitors, sacituzumab, others) as appropriate per NCCN
Gastric/GEJ cancer — trastuzumab‑based regimens	Trastuzumab‑based combination regimens (examples per NCCN/Appendix B) — recommended prior to Enhertu for this indication
NSCLC — systemic chemotherapy/targeted therapies	Platinum‑based regimens ± immunotherapy (eg, carboplatin/pemetrexed ± pembrolizumab), or other targeted agents when appropriate per molecular profile
Other tumor types (cervical, salivary gland, endometrial) — NCCN‑recommended options	Tumor‑specific first‑line and subsequent therapies per NCCN (eg, platinum‑based doublets, topotecan, paclitaxel, bevacizumab, tisotumab vedotin, cemiplimab, etc.) — may be required depending on line of business and formulary status

Situation	Policy statement
HR‑positive HER2‑low breast cancer with visceral crisis	Per NCCN‑aligned policy update, prior endocrine therapy requirement may be bypassed when the member is experiencing visceral crisis
HR‑positive HER2‑low breast cancer without visceral crisis	Standard prior therapy requirement applies: failure of ≥1 prior line of chemotherapy plus endocrine therapy for HR‑positive disease unless ineligible

Coding and Dose Limits

HCPCS CodesHCPCS

J9358

Injection, fam-trastuzumab deruxtecan-nxki, 1 mg

inv-10: Maximum Dose

Maximum dose — breast, NSCLC, IHC 3+ solid tumors5.4 mg/kg (IV) every 3 weeks — maximum 5.4 mg/kg

Maximum dose — gastric/GEJ cancer6.4 mg/kg (IV) every 3 weeks — maximum 6.4 mg/kg

Dosing intervalAdministered IV every 3 weeks for all indications listed

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation demonstrating diagnosis, prior therapies, prescriber specialty, age, and dosing within policy limits. Prior authorization may be implied by the clinical policy framework when coverage is governed by this policy or for newly approved/expanded indications.

A prior authorization request must show the requested dose is within the specified limits (e.g., ≤5.4 mg/kg q3w for most indications; ≤6.4 mg/kg q3w for gastric/GEJ when applicable) or be supported by practice guidelines/peer-reviewed literature for off‑label use.

Documentation Required

Providers must submit supporting documentation (e.g., office chart notes, relevant lab results, pathology reports, imaging, prior treatment records) that demonstrates the member meets ALL approval criteria. Failure to submit adequate documentation may result in denial.

Include documentation of diagnosis, oncologist involvement or consultation, member age, prior lines of therapy and dates, response assessments, and dosing rationale.

Background

Enhertu (fam‑trastuzumab deruxtecan‑nxki) is a HER2‑directed antibody‑drug conjugate linked to a topoisomerase I inhibitor payload. It is indicated for multiple HER2‑expressing or HER2‑mutant malignancies, including unresectable or metastatic HER2‑positive breast cancer, HER2‑low breast cancer after prior chemotherapy, HER2‑mutant non‑small cell lung cancer, and HER2‑positive gastric/gastroesophageal junction adenocarcinoma; the product is supplied as a 100 mg single‑dose vial. The policy has been updated to add indications such as adjuvant use in rectal cancer and expanded criteria for certain IHC 3+ solid tumors and selected off‑label malignancies.

Definitions and Key Terms

inv-24: Agent description — Enhertu (fam-trastuzumab deruxtecan-nxki)

Generic namefam-trastuzumab deruxtecan-nxki

Brand nameEnhertu

MechanismHER2-directed antibody-drug conjugate with a topoisomerase inhibitor payload (HER2-directed ADC)

inv-25: HER2-low

DefinitionHER2-low is defined as IHC 1+ OR IHC 2+ with ISH-negative as determined by an FDA-approved test

ContextApplies to selection of patients with unresectable or metastatic HER2-low breast cancer for Enhertu therapy

Testing requirement

Quantity Limits and Product Availability

inv-38: fam-trastuzumab deruxtecan-nxki — Single‑dose vial: 100 mg

Package formSingle-dose vial: 100 mg lyophilized powder

Product namefam-trastuzumab deruxtecan-nxki (Enhertu)

UseVial size for preparation of IV doses as specified in dosing guidance

Site of Care

Note

Site of care not specified here

Site of care for administration is not specifically restricted in this policy section.