Pemetrexed — CPB 0687 | AETNA Coverage Update

Aetna modified CPB 0687 for pemetrexed, effective February 25, 2026. Here's what billing teams need to know before submitting claims under J9305 and related codes.

Aetna updated its pemetrexed coverage policy under CPB 0687, effective February 25, 2026. The policy was modified — billing teams should review all covered indications and regimen criteria against the updated policy before submitting claims. The policy governs pemetrexed billing across brand names Alimta, Axtle, Pemfexy, Pemrydi RTU, and generics billed under HCPCS codes J9292 through J9324. If your oncology or infusion billing team submits claims for pemetrexed infusions paired with CPT codes 96413, 96415, and 96417, this update changes what you need to document before the claim goes out.

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Quick-Reference Table

Field	Detail Copy
Payer	Aetna
Policy	Pemetrexed — CPB 0687
Policy Code	CPB 0687
Change Type	Modified
Effective Date	February 25, 2026
Impact Level	High
Specialties Affected	Medical oncology, infusion therapy, thoracic surgery, gynecologic oncology, urology, neurology (CNS lymphoma)
Key Action	Audit documentation and prior authorization requests to confirm histology, regimen, and indication match the updated criteria before submitting claims

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Aetna Pemetrexed Coverage Criteria and Medical Necessity Requirements 2026

Aetna's pemetrexed coverage policy under CPB 0687 ties medical necessity directly to cancer histology and treatment regimen. Getting this wrong means a claim denial—and pemetrexed infusions are not cheap.

The core rule hasn't changed: squamous cell non-small cell lung cancer (NSCLC) is excluded. Full stop. If a patient has squamous NSCLC, pemetrexed is not covered under this policy regardless of regimen. For non-squamous NSCLC—including leptomeningeal metastases—coverage applies without additional regimen restrictions.

Mesothelioma criteria got more specific. Aetna now covers pemetrexed for pleural or peritoneal mesothelioma (including pericardial mesothelioma and tunica vaginalis testis mesothelioma) across three distinct regimen tracks:

#	Covered Indication Copy
1	Single agent, or in combination with cisplatin (J9060) or carboplatin (J9045 or C9308)
2	In combination with bevacizumab (J9035 or Q5107) or durvalumab plus cisplatin or carboplatin
3	As first-line therapy in combination with pembrolizumab (J9271) and platinum chemotherapy

The pembrolizumab combination is the notable addition. This first-line pembrolizumab plus platinum track comes with a 24-month continuation cap—document this in your system now so you're not approving continued therapy past the limit.

Thyroid cancer criteria are layered. Aetna covers pemetrexed for three distinct thyroid histologies, each with separate requirements:

#	Covered Indication Copy
1	Papillary or follicular thyroid carcinoma: Disease must be unresectable or metastatic, not amenable to radioactive iodine (RAI) therapy, and pemetrexed must be used with carboplatin
2	Oncocytic/Hürthle cell thyroid carcinoma: Disease must be unresectable or metastatic, combined with carboplatin
3	Anaplastic carcinoma: Disease must be metastatic, combined with carboplatin, and only after progression following prior treatment

The source policy does not specify prior authorization requirements. Contact Aetna directly to confirm PA requirements before submitting claims for any thyroid cancer indication. Your authorization request must document the specific histology, the RAI amenability determination (for papillary/follicular), and the confirmed carboplatin combination plan.

Other covered indications include:

Medical necessity documentation must match the indication precisely. "Lung cancer" without histology confirmation is not sufficient for a non-squamous NSCLC claim.

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Aetna Pemetrexed Exclusions and Non-Covered Indications

Squamous cell NSCLC is the hard exclusion. Aetna will not cover pemetrexed for this histology. This is a long-standing restriction, not new to this update—but it still drives claim denials when histology isn't confirmed in the documentation.

All indications not listed in Section II of CPB 0687 are considered experimental, investigational, or unproven. Aetna treats "not listed" the same as "excluded." If a clinical team is using pemetrexed off the covered indication list, expect denial without a strong medical necessity appeal.

HCPCS code 81291—MTHFR gene analysis—is specifically listed as not covered under this policy, even when pemetrexed is the primary agent. Don't bundle that code expecting coverage.

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Coverage Indications at a Glance

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Aetna Pemetrexed Billing Guidelines and Action Items 2026

These steps apply now. The effective date is February 25, 2026—if you're reading this after that date, audit retroactively for claims submitted without updated documentation.

Copy Action Items

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CPT, HCPCS, and ICD-10 Codes for Pemetrexed Under CPB 0687

Covered HCPCS Codes (When Selection Criteria Are Met)

Not Covered HCPCS Codes

Code	Description	Reason Copy
81291	MTHFR gene analysis (hereditary hypercoagulability)	Explicitly excluded under CPB 0687 selection criteria

IV Infusion Administration CPT Codes

Key ICD-10-CM Diagnosis Codes

Note: The full policy references 181 ICD-10-CM codes. The table above reflects the codes explicitly provided in the CPB 0687 policy data. Review the full code list at the Aetna CPB 0687 source document to confirm all applicable diagnosis codes for your patient population.

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