Pharmacogenetic Testing — CPB 0715 | AETNA Coverage Update

Aetna modified CPB 0715 for pharmacogenetic testing, effective December 4, 2025. Here's what billing teams need to know before submitting claims.

Aetna, a CVS Health company, updated its pharmacogenetic testing coverage policy under CPB 0715 in Aetna's clinical policy bulletin system. This policy governs a large set of molecular and genomic tests — 159 CPT codes in total — including commonly billed codes like 81225 (CYP2C19), 81226 (CYP2D6), 81232 (DPYD), and dozens of oncology-specific panels. The update draws sharper lines between what qualifies for reimbursement and what Aetna considers not medically necessary, including explicit exclusions for broad FoundationOne panel testing in several cancer indications where targeted testing is sufficient.

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Quick-Reference Table

Field	Detail Copy
Payer	Aetna (CPB 0715 Aetna system)
Policy	Pharmacogenetic Testing — CPB 0715
Policy Code	CPB 0715
Change Type	Modified
Effective Date	December 4, 2025
Impact Level	High
Specialties Affected	Oncology, psychiatry, neurology, infectious disease, hematology, pain management
Key Action	Audit charge capture for FoundationOne CDx and Liquid CDx codes before billing against oncology indications — Aetna has added explicit "not medically necessary" language for several targeted uses

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Aetna Pharmacogenetic Testing Coverage Criteria and Medical Necessity Requirements 2025

Aetna's pharmacogenetic testing coverage policy under CPB 0715 is indication-specific. That's the most important thing to understand here. A test that's covered for one drug or cancer type will be denied for another — even if the CPT code is identical.

The policy lists dozens of covered indications tied to specific drugs and diagnoses. Covered tests must meet medical necessity criteria: the member must be a candidate for a specific drug, and the test must be the appropriate targeted assay — not a broad panel — unless the panel is specifically listed as covered.

Oncology Indications

For NSCLC, Aetna covers ALK fusion gene testing (e.g., Vysis ALK Break Apart FISH Probe Kit, Ventana ALK CDx Assay) for members considering crizotinib (Xalkori), alectinib (Alecensa), or ceritinib (Zykadia). ALK gene rearrangement testing is also covered for pembrolizumab (Keytruda) candidacy.

BRAF V600E and V600K mutation testing is covered across four tumor types. For unresectable or metastatic melanoma, covered drugs include vemurafenib (Zelboraf), dabrafenib (Tafinlar), trametinib (Mekinist), cobimetinib (Cotellic), binimetinib (Mektovi), and encorafenib (Braftovi). For metastatic colorectal cancer, encorafenib candidacy supports BRAF testing. For recurrent or metastatic NSCLC, dabrafenib, pembrolizumab, or vemurafenib trigger eligibility. For thyroid carcinoma, dabrafenib or vemurafenib candidacy qualifies.

BRCA testing is covered for multiple indications — advanced epithelial ovarian cancer, fallopian tube and primary peritoneal cancer, metastatic pancreatic carcinoma, and others — when members are being considered for targeted therapies like olaparib (Lynparza). The BRACAnalysis CDx is specifically referenced as a covered assay.

BRAF and NRAS mutations (CPT 81311) are covered for colorectal cancer members considering cetuximab (Erbitux) or panitumumab (Vectibix).

Drug Metabolism (PGx) Indications

CYP2D6 testing (CPT 81226, plus PLA codes 0028U, 0070U–0076U) and CYP2C19 testing (CPT 81225) are covered when medical necessity criteria tie the test to a specific drug metabolism indication. DPYD testing (CPT 81232) is covered for members being considered for 5-fluorouracil or capecitabine — a test your oncology billing team should have on their standard checklist.

MGMT methylation analysis (CPT 81287) is covered for glioblastoma multiforme. IDH1 (CPT 81120) and IDH2 (CPT 81121) testing is covered for glioma indications.

FLT3 internal tandem duplication testing (CPT 81245) and TKD variants (CPT 81246) are covered for acute myeloid leukemia when members are candidates for FLT3 inhibitors. EZH2 testing (CPT 81236, 81237) is covered for myelodysplastic syndrome, myeloproliferative neoplasms, and diffuse large B-cell lymphoma.

KIT gene testing (CPT 81272) is covered for gastrointestinal stromal tumor members considering imatinib or sunitinib. KRAS additional variant testing (CPT 81276) and NRAS (CPT 81311) are covered for colorectal cancer indications. PIK3CA testing (CPT 81309, 0155U, 0177U) is covered for breast and colorectal cancer indications.

HCV genotyping (CPT 87902) is covered for hepatitis C members being considered for antiviral treatment. HCV drug susceptibility phenotype prediction (CPT 87900) is also covered under specified criteria.

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Aetna Pharmacogenetic Testing Exclusions and Non-Covered Indications

This is where the policy change has the most billing impact. Aetna draws a hard line against broad genomic panels when targeted testing is sufficient.

FoundationOne CDx and FoundationOne Liquid CDx are not medically necessary for several specific indications listed in this policy. This is not ambiguous language — Aetna states directly there is "no proven advantage" of these panels over targeted testing in the following situations:

#	Excluded Procedure Copy
1	FoundationOne CDx and FoundationOne Liquid CDx for ALK mutation testing in NSCLC members being considered for alectinib (Alecensa)
2	FoundationOne Liquid CDx for BRAF V600E mutation testing in melanoma members being considered for encorafenib (Braftovi)
3	FoundationOne CDx and FoundationOne Liquid CDx for BRCA mutation testing in ovarian cancer members being considered for olaparib (Lynparza)

CPT 0037U (FoundationOne CDx, 324-gene solid tumor panel) and CPT 0239U/0242U (liquid biopsy panels) appear in the covered code list — but only when selection criteria are met. If your team is billing these codes for the indications above, expect claim denial.

Aetna also considers the following categories not covered under this CPB:

The psychiatric genomic panel exclusions deserve a call-out. CPT 0173U and 0175U — both depression/anxiety genomic panels — are explicitly not covered. If your psychiatry or primary care billing team has been submitting these, stop before the December 4, 2025 effective date. Those claims will not survive review.

The broader Aura Genetics EffectiveRX panel codes (CPT 0347U–0350U, 0419U, 0434U, 0437U, 0438U, 0460U, 0461U, plus 0289U and 0294U for Alzheimer/longevity RNA profiling) are listed separately in the policy under their own group designation. Review the full CPB 0715 and your plan-level documentation to determine applicable coverage requirements for these codes.

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Coverage Indications at a Glance

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Aetna Pharmacogenetic Testing Billing Guidelines and Action Items 2025

The effective date is December 4, 2025. Here's what to do before then.

Copy Action Items

If your practice has a complex oncology or psychiatry PGx billing mix, loop in your compliance officer before the December 4 effective date. The indication-drug linkage requirements in this policy are detailed enough that a systematic audit is worth the time.

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CPT, HCPCS, and ICD-10 Codes for Pharmacogenetic Testing Under CPB 0715

Covered CPT Codes (When Selection Criteria Are Met)

Not Covered / Experimental CPT Codes

Aura Genetics EffectiveRX Panel Codes (Grouped Separately — Review Full Policy)

These codes are grouped separately in the policy under the Aura Genetics EffectiveRX designation. Review the full CPB 0715 and your plan-level documentation to determine applicable coverage requirements.

Note: The full policy includes 159 CPT codes. The codes listed here represent all codes provided in the policy data. Review the full CPB 0715 at app.payerpolicy.org/p/aetna/0715 for the complete list and ICD-10-CM diagnosis codes (1,169 total).

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