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.

Aetna, a CVS Health company, updated its pemetrexed coverage policy under CPB 0687 Aetna system, covering indications across nine cancer types billed under HCPCS codes J9292 through J9324 and administered via CPT 96413, 96415, and related infusion codes. The update expands covered indications and adds specific combination therapy criteria — particularly for mesothelioma with pembrolizumab (J9271) — that your prior authorization requests must reflect. If your oncology or hematology billing team hasn't mapped these changes yet, denials are coming.

Quick-Reference Table

Aetna Pemetrexed Coverage Criteria and Medical Necessity Requirements 2026

Aetna's pemetrexed coverage policy under CPB 0687 covers nine distinct cancer types — but each carries its own medical necessity criteria, and getting them wrong means claim denial.

The coverage policy requires histology-specific documentation for NSCLC. Pemetrexed is covered only for non-squamous NSCLC, including leptomeningeal metastases. Squamous cell NSCLC is a hard exclusion, full stop.

For mesothelioma, Aetna now covers pemetrexed in four distinct regimen configurations. Single-agent or platinum combination (cisplatin, J9060, or carboplatin, J9045) remains covered. Bevacizumab (J9035 or biosimilar Q5107) or durvalumab with platinum is covered. First-line pemetrexed plus pembrolizumab (J9271) plus platinum chemotherapy is now also covered — and continuation of that regimen has a 24-month cap built into the policy.

That 24-month cap on pemetrexed plus pembrolizumab for mesothelioma is new. Your charge capture system and prior authorization tracking need to flag claims approaching that ceiling before Aetna does it for you.

Thyroid cancer coverage under this policy is the most criteria-dense section. Three thyroid subtypes are covered — papillary/follicular, oncocytic/Hürthle cell, and anaplastic — but each subtype has a different set of required conditions. Anaplastic carcinoma requires metastatic disease and prior treatment failure. Papillary/follicular requires unresectable or metastatic disease, RAI ineligibility, and carboplatin combination. Miss one of those criteria in your clinical documentation and the claim fails.

Vaginal cancer is a narrower indication: subsequent-line only, recurrent or metastatic, single agent. First-line vaginal cancer claims will not meet medical necessity under this policy.

Prior authorization is required for pemetrexed reimbursement across all covered indications. Document the specific regimen — single agent versus combination — in every prior auth request. Aetna's criteria are regimen-specific, and a prior auth for single-agent pemetrexed won't cover a combination claim.

Aetna Pemetrexed Exclusions and Non-Covered Indications

The squamous cell NSCLC exclusion is the one that will generate the most denials. Pemetrexed is well-known in lung cancer, and it's easy for a billing team to code NSCLC without confirming the histology subtype first.

Aetna considers all indications not listed in the approved criteria experimental, investigational, or unproven. That's a broad exclusion with real financial exposure. If your oncologists are using pemetrexed off-label for a diagnosis not on this list, expect denial and no viable appeal path under this policy.

HCPCS code 81291 (MTHFR gene analysis) is explicitly listed as not covered under this policy. Don't bill it in combination with pemetrexed claims expecting bundled coverage.

Coverage Indications at a Glance

Aetna Pemetrexed Billing Guidelines and Action Items 2026

If your patient mix includes a high volume of mesothelioma or thyroid cancer cases, loop in your compliance officer before the effective date of February 25, 2026. The multi-criteria thyroid indications and the 24-month mesothelioma cap both create audit exposure if your documentation workflows aren't updated.

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

Covered HCPCS Codes (When Selection Criteria Are Met)

Not Covered / Experimental Codes

Key ICD-10-CM Diagnosis Codes

This policy references 181 ICD-10-CM codes in total. The complete code list is available in the full policy at CPB 0687 on app.payerpolicy.org.