Trastuzumab (Herceptin and biosimilars), Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta) — CPB 0313 | AETNA Coverage Update

TL;DR: Aetna, a CVS Health company, modified CPB 0313 covering trastuzumab (Herceptin and biosimilars) and trastuzumab and hyaluronidase-oysk (Herceptin Hylecta), effective January 22, 2026. Here's what billing teams need to do.

This update to Aetna's trastuzumab coverage policy under CPB 0313 Aetna system expands approved indications across multiple tumor types—breast, colorectal, biliary tract, salivary gland, and uterine cancers. If your practice bills chemotherapy administration codes like CPT 96413 or infusion codes like CPT 96365 for any trastuzumab product, this change affects your prior authorization criteria and your medical necessity documentation today.

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Quick-Reference Table

Field	Detail Copy
Payer	Aetna, a CVS Health company
Policy	Trastuzumab (Herceptin and biosimilars), Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta)
Policy Code	CPB 0313
Change Type	Modified
Effective Date	January 22, 2026
Impact Level	High
Specialties Affected	Oncology, hematology/oncology, infusion centers, hospital outpatient, specialty pharmacy
Key Action	Verify HER2 testing documentation, RAS/BRAF mutation status (colorectal), and combination therapy partners before submitting prior auth requests after January 22, 2026

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Aetna Trastuzumab Coverage Criteria and Medical Necessity Requirements 2026

The real issue here is scope. Aetna's CPB 0313 now covers trastuzumab across six distinct cancer types. Each indication has its own set of medical necessity criteria. Getting any one element wrong triggers a claim denial.

Precertification is required for all products under this policy. Call (866) 752-7021 or fax the SMN precertification form to (888) 267-3277. This applies to every trastuzumab product listed—Herceptin, Hercessi (trastuzumab-strf), Herzuma (trastuzumab-pkrb), Kanjinti (trastuzumab-anns), Ogivri (trastuzumab-dkst), Ontruzant (trastuzumab-dttb), and Trazimera (trastuzumab-qyyp).

A site-of-care utilization management policy also applies to all IV trastuzumab formulations. If your patients are receiving infusions outside a hospital outpatient setting, review Aetna's Site of Care for Specialty Drug Infusions policy before billing CPT 96365 or 96366.

Breast Cancer Criteria

Aetna covers trastuzumab for HER2-positive breast cancer in four settings:

There's a fifth breast cancer indication that many teams will miss. Trastuzumab is covered for HER2-negative metastatic breast cancer when used in combination with neratinib and fulvestrant as third-line or later therapy. That's not a typo. HER2-negative. Make sure your medical necessity documentation spells out the combination and line of therapy explicitly.

Colorectal Cancer Criteria

This is the most documentation-intensive indication in the policy. All four criteria must be met:

This applies to colorectal cancer, appendiceal adenocarcinoma, and anal adenocarcinoma. If your molecular diagnostic documentation doesn't confirm both RAS and BRAF wild-type status, Aetna will deny the claim. Your CPT 83890–83914 (molecular diagnostics) and CPT 88271–88275 (molecular cytogenetics) results need to be in the record.

Other Approved Tumor Types

Esophageal, gastric, or gastroesophageal junction cancer: HER2-positive disease in combination with chemotherapy, including palliative settings.

Biliary tract cancers: Subsequent treatment of unresectable, resected gross residual (R2), or metastatic HER2-positive disease confirmed by IHC 3+, ISH+, or NGS amplification. Must be used in combination with pertuzumab or tucatinib. This covers intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer.

Salivary gland tumors: Recurrent, unresectable, or metastatic HER2-positive tumors. Covered as a single agent or in combination with docetaxel or pertuzumab.

Uterine serous carcinoma or carcinosarcoma: HER2-positive stage III–IV, recurrent, or metastatic disease. Must be used in combination with carboplatin and paclitaxel, then continued as single-agent maintenance therapy.

Each of these indications requires HER2 testing documentation. CPT codes 88341–88344 (immunohistochemistry), 88360–88377 (morphometric analysis and in situ hybridization), cover that testing. Make sure your pathology reports reference the specific IHC or ISH result that matches the policy threshold for the relevant indication.

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Aetna Trastuzumab Exclusions and Non-Covered Indications

The policy summary notes that all indications not explicitly listed are considered experimental, investigational, or unproven. That's standard Aetna language—but it matters here because trastuzumab gets tried off-label across many tumor types.

If your oncologist is using trastuzumab for a tumor type not on the approved list, expect a denial. The policy doesn't leave wiggle room on this. Document the clinical rationale and loop in your compliance officer before submitting those claims.

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Coverage Indications at a Glance

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Aetna Trastuzumab Billing Guidelines and Action Items 2026

Copy Action Items

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CPT, HCPCS, and ICD-10 Codes for Trastuzumab Under CPB 0313

Covered CPT Codes (When Selection Criteria Are Met)

HER2 Testing — Molecular Diagnostics

HER2 Testing — Molecular Cytogenetics and Pathology

Drug Administration — Infusion and Injection

Note: The policy data references 20 additional CPT codes beyond those listed above. Review the full CPB 0313 policy at the Aetna source for the complete list.

Note: The policy data references 19 HCPCS codes and 246 ICD-10-CM codes. The full code sets were not included in the policy summary provided. Review the complete CPB 0313 document for all applicable HCPCS and ICD-10-CM codes before updating your charge capture.

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