Fam-trastuzumab Deruxtecan-nxki (Enhertu) — CPB 0966 | AETNA Coverage Update

Aetna modified CPB 0966 for fam-trastuzumab deruxtecan-nxki (Enhertu), effective January 23, 2026. Here's what billing teams need to know.

Aetna, a CVS Health company, updated its Enhertu coverage policy under CPB 0966 on January 23, 2026. This policy governs HCPCS code J9358 (fam-trastuzumab deruxtecan-nxki, 1 mg) for commercial plan members across a broad range of solid tumor indications — including breast cancer, non-small cell lung cancer, biliary tract cancer, and gastroesophageal adenocarcinoma. If your oncology or infusion team bills J9358 through Aetna commercial plans, this update changes the medical necessity criteria your precertification requests need to satisfy.

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Quick-Reference Table

Field	Detail Copy
Payer	Aetna, a CVS Health company
Policy	Fam-trastuzumab Deruxtecan-nxki (Enhertu)
Policy Code	CPB 0966
Change Type	Modified
Effective Date	January 23, 2026
Impact Level	High
Specialties Affected	Medical Oncology, Hematology/Oncology, Infusion Services, Hospital Outpatient Oncology
Key Action	Audit active Enhertu precertification requests against updated HER2 status and line-of-therapy criteria before submitting new prior auth requests

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Aetna Enhertu Coverage Criteria and Medical Necessity Requirements 2026

Aetna requires precertification for every Enhertu claim under commercial plan designs. There are no exceptions. Call (866) 752-7021 or fax (888) 267-3277 to initiate precertification. Statement of Medical Necessity forms are available through Aetna's Specialty Pharmacy Precertification portal.

The coverage policy under CPB 0966 Aetna system defines medical necessity across five main tumor types. Each carries distinct criteria. Get them wrong on the prior auth and you're looking at a claim denial before the drug ever ships.

Breast Cancer

Aetna covers Enhertu for breast cancer under four distinct HER2 expression categories. Each has its own criteria, and they are not interchangeable.

HER2-positive breast cancer: Aetna considers Enhertu medically necessary when the disease had no response to preoperative systemic therapy, or the disease is recurrent, metastatic, or unresectable. The drug must be used as a single agent.

HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-): Same disease-stage criteria apply. The drug must be used as a single agent. The IHC classification here is critical — your documentation needs to show the exact IHC result from pathology.

HER2-ultralow breast cancer (IHC 0 with membrane staining): This is the most restrictive tier. The disease must be recurrent, metastatic, or unresectable. It must also be hormone receptor positive with visceral crisis or endocrine therapy refractory — or hormone receptor negative. Single-agent use only. Documentation of the IHC 0 membrane staining finding is required.

HER2-negative breast cancer: Coverage applies when the disease had no response to preoperative systemic therapy, or is recurrent, unresectable, or metastatic — and is hormone receptor positive with visceral crisis or endocrine therapy refractory. This indication has an additional line-of-therapy requirement: Enhertu must be used as first-line therapy. Miss that detail and prior authorization will fail.

Non-Small Cell Lung Cancer

For NSCLC with HER2 (ERBB2) mutations or HER2 overexpression (IHC 3+), Aetna covers Enhertu as subsequent therapy only. Three criteria must all be met:

#	Covered Indication Copy
1	The disease is recurrent, advanced, metastatic, or unresectable.
2	The drug is used as a single agent.
3	The member has not experienced disease progression on a HER2-targeted drug — specifically called out is Kadcyla (ado-trastuzumab emtansine, J9354).

That third criterion is the one most likely to trip up a prior auth submission. If your patient previously progressed on Kadcyla, coverage is denied under this indication. Confirm treatment history before submitting.

Biliary Tract Cancer

Aetna covers Enhertu for subsequent treatment of unresectable or resected gross residual (R2) disease or metastatic biliary tract cancer — including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. The tumor must be HER2-positive at IHC 3+. Single-agent use only. The IHC threshold here is higher than the breast cancer HER2-low category, so confirm pathology reports carefully.

Esophageal, Gastric, or Gastroesophageal Junction Adenocarcinoma

For HER2-positive esophageal, gastric, or gastroesophageal junction adenocarcinoma, Aetna covers Enhertu as a single agent for members who are not surgical candidates, or as subsequent treatment for unresectable locally advanced, recurrent, or metastatic disease. The prior authorization request should specify surgical candidacy status or prior treatment history clearly.

Solid Tumors (Tumor-Agnostic Indication)

Aetna also covers Enhertu for solid tumors generally when the disease is unresectable, metastatic, advanced, recurrent, or persistent, and the tumor is HER2-positive at IHC 3+ or IHC 2+. This is the broadest coverage pathway under CPB 0966 — but the IHC documentation requirement still applies. Without it, expect a denial.

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Aetna Enhertu Exclusions and Non-Covered Indications

The policy data does not enumerate a standalone exclusions list in the truncated summary provided. However, several implicit non-coverage conditions emerge from the criteria:

If you have patients on Enhertu combination regimens, or patients with ambiguous HER2 results, loop in your compliance officer before submitting a prior auth under CPB 0966. The criteria are specific enough that off-label combinations will trigger denial.

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Coverage Indications at a Glance

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Aetna Enhertu Billing Guidelines and Action Items 2026

The January 23, 2026 effective date is already past. If you haven't audited your active Enhertu cases against the updated CPB 0966 criteria, do it now.

Copy Action Items

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CPT, HCPCS, and ICD-10 Codes for Enhertu Under CPB 0966

Covered HCPCS Code (When Selection Criteria Are Met)

Code	Type	Description Copy
J9358	HCPCS	Injection, fam-trastuzumab deruxtecan-nxki, 1 mg

J9358 is the primary billing code for Enhertu. Every covered indication in CPB 0966 routes through this code. Bill per milligram administered.

Other HCPCS Codes Referenced in CPB 0966

Code	Type	Description	Note Copy
J9354	HCPCS	Injection, ado-trastuzumab emtansine, 1 mg (Kadcyla)	Referenced in NSCLC exclusion criteria — prior use of this agent disqualifies coverage under NSCLC pathway

Chemotherapy Administration CPT Codes

Aetna's CPB 0966 references CPT codes 96401 through 96450 for chemotherapy administration. These codes cover the infusion and injection services associated with Enhertu administration. The correct administration code depends on route, duration, and facility setting. Work with your coding team to match the appropriate CPT to each encounter.

Code Range	Type	Description Copy
96401–96450	CPT	Chemotherapy administration (see full list below)

Full CPT Code List:

Key ICD-10-CM Diagnosis Codes

CPB 0966 references 793 ICD-10-CM codes. The policy covers a wide range of solid tumor primary sites. Below are the codes included in the policy data provided:

The full list of 793 ICD-10-CM codes spans malignancies from salivary glands and nasopharynx through breast, lung, gastric, biliary, and broader solid tumor histologies. Run your ICD-10 codes against the full CPB 0966 code list before submitting. An unsupported diagnosis code is one of the most common preventable claim denial triggers on high-cost oncology drugs.

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