CurrentEmblemHealthPolicy N/A

Pemetrexed (Alimta/Pemfexy/Axtle/Pemrydi) — Coverage Criteria

Defines accepted indications, contraindications, exclusions, and coding for pemetrexed products for treatment of malignant pleural mesothelioma and non-small cell lung cancer; applies to providers submitting medication requests to Evolent for EmblemHealth lines of business.

Policy Summary

PayerEmblemHealth

PolicyPemetrexed (Alimta/Pemfexy/Axtle/Pemrydi) — Coverage Criteria

Policy CodePolicy N/A

Change TypeClinical + Administrative

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization supported by FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature when requesting pemetrexed.

SourceLink

POLICY UPDATE CHANGES

Updated NSCLC indication to allow maintenance therapy with durvalumab +/- pemetrexed after first-line therapy with platinum-based chemotherapy, tremelimumab, and durvalumab if restaging shows stability or response.

Added use with pembrolizumab and platinum chemotherapy to MPM indication section.

Added use with amivantamab (Rybrevant) and carboplatin for EGFR exon 20 insertion mutations and for select EGFR-mutant disease after progression on TKIs.

Added new brand names 'Axtle' and 'Pemrydi' to relevant sections.

2Primary tumor types addressed (MPM, NSCLC)

≥9Listed HCPCS codes for pemetrexed products

500 mg/m2

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria for Pemetrexed Products

Malignant Pleural Mesothelioma - Covered Indications

Covered when ANY of the following are met:

MPM indications: In combination with cisplatin or carboplatin for stage I-IIIA clinically operable disease; In combination with pembrolizumab (Keytruda) and cisplatin or carboplatin as first-line treatment of unresectable advanced or metastatic disease; As first-line therapy for unresectable or metastatic disease as a single agent or in combination with cisplatin or carboplatin with or without bevacizumab; As subsequent therapy as a single agent if pemetrexed was not used previously in the first-line setting.

Per policy, J9304 (Pemfexy) is not supported for MPM due to lack of Level 1 evidence comparing pemetrexed products.

Non-Small Cell Lung Cancer - Covered Indications

Covered when ANY of the following are met for recurrent or metastatic non-squamous NSCLC:

NSCLC indications list: First-line therapy with carboplatin or cisplatin; First-line therapy with carboplatin or cisplatin plus pembrolizumab (Keytruda) for EGFR‑negative and ALK‑negative disease; First-line therapy with amivantamab (Rybrevant) plus carboplatin for EGFR exon 20 insertion mutations; Subsequent therapy in combination with carboplatin or cisplatin; Subsequent therapy with amivantamab plus carboplatin for select EGFR mutations (exon 19 deletions or exon 21 L858R); Subsequent therapy as single-agent pemetrexed; Maintenance single-agent pemetrexed after response or stable disease following first-line chemotherapy; Maintenance in combination with pembrolizumab following first-line pembrolizumab + pemetrexed + platinum; First-line combination of durvalumab (Imfinzi) + tremelimumab (Imjudo) + platinum chemotherapy for EGFR‑ and ALK‑negative metastatic or stage IV disease (may be followed by maintenance durvalumab ± pemetrexed).

Certain regimens are specifically not supported per policy (see exclusions and NOT_SUPPORTED regimen list).

Regimen	Indication	Coverage
Pemetrexed + cisplatin or carboplatin
Indication: Stage I–IIIA clinically operable malignant pleural mesothelioma (in combination with platinum)
Covered when used as listed per policy
Pemetrexed + pembrolizumab + cisplatin or carboplatin
Indication: First-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma
Covered when used as listed per policy
Pemetrexed as a single agent
Indication: First-line therapy for unresectable or metastatic disease, or subsequent single-agent therapy if not used first-line
Covered when used as listed per policy
Pemetrexed ± bevacizumab with cisplatin or carboplatin
Indication: First-line therapy for unresectable or metastatic disease (with or without bevacizumab)
Covered when used as listed per policy

Regimen	Line / Biomarker context	Coverage
Pemetrexed with carboplatin or cisplatin
Line: First-line or subsequent therapy for recurrent/metastatic non-squamous NSCLC
Covered when used per policy
Pemetrexed + pembrolizumab + platinum (carboplatin or cisplatin)
Line/Biomarker: First-line for EGFR-negative and ALK-negative non-squamous NSCLC
Covered when used per policy
Pemetrexed + amivantamab (Rybrevant) + carboplatin
Biomarker: For tumors with EGFR exon 20 insertion mutations
Covered when used per policy
Maintenance pemetrexed (single-agent)
Context: After response or stable disease following first-line chemotherapy; may follow certain first-line regimens per policy
Covered when used per policy
Durvalumab + tremelimumab + platinum induction followed by maintenance durvalumab ± pemetrexed
Line/Biomarker: First-line for EGFR-/ALK- metastatic or stage IV non-squamous NSCLC; maintenance permitted after restaging shows response or stability
Covered when used per policy

Regimen	Rationale / Context	Coverage
Bevacizumab + carboplatin or cisplatin + pemetrexed followed by maintenance bevacizumab + pemetrexed
Note: Listed by policy as not supported due to lack of Level 1 evidence demonstrating superiority compared to recommended alternatives
Not supported per policy (regimen lacks Level 1 evidence)
Nivolumab + ipilimumab + carboplatin or cisplatin + pemetrexed followed by maintenance nivolumab + ipilimumab (for PD-L1 ≥1%)
Note: Listed by policy as not supported based on lack of Level 1 evidence; PD-L1 context noted in source
Not supported per policy (regimen lacks Level 1 evidence)

Requests will be denied or are excluded when any of the following apply: dosing that exceeds a single-dose maximum of 500 mg/m2; documented disease progression on pemetrexed or a pemetrexed-containing regimen; use of pemetrexed for squamous cell NSCLC; or investigational/off‑label use that lacks sufficient supporting evidence or is not generally accepted by the medical community (i.e., not supported by CMS‑recognized compendia or acceptable peer‑reviewed literature).

Certain combination regimens that lack Level 1 evidence demonstrating superior outcomes compared with recommended alternatives are not supported. Examples called out include nivolumab + ipilimumab + carboplatin/cisplatin + pemetrexed followed by maintenance nivolumab + ipilimumab (noted when PD‑L1 ≥1%). Additionally, the policy specifies that particular proprietary pemetrexed products (e.g., J9304 Pemfexy) are not supported for NSCLC when Level 1 evidence is absent showing product‑specific superiority.

Billing and Coding

HCPCS codes for pemetrexed productsHCPCS

J9292	Injection, pemetrexed dipotassium, 10 mg
J9294	Injection, pemetrexed (hospira), not therapeutically equivalent to j9305, 10 mg
J9296	Injection, pemetrexed (accord), not therapeutically equivalent to j9305, 10 mg
J9297	Injection, pemetrexed (sandoz), not therapeutically equivalent to j9305, 10 mg
J9304	Injection, pemetrexed (pemfexy), 10 mg
J9305	Injection, pemetrexed, not otherwise specified, 10 mg
J9314	Injection, pemetrexed (teva), not therapeutically equivalent to j9305, 10 mg
J9322	Injection, pemetrexed (bluepoint), not therapeutically equivalent to j9305, 10 mg
J9323	Injection, pemetrexed ditromethamine, 10 mg
J9324	Injection, pemetrexed (pemrydi rtu), 10 mg

inv-06: Single-dose maximum — 500 mg/m2

Single-dose maximum500 mg/m2

Applies toAlimta/Pemfexy/Axtle/Pemrydi (pemetrexed) products

Consequence of exceedanceRequests exceeding this single-dose limit may be denied per policy exclusion criteria

Provider Actions and Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for all requests for Alimta/Pemfexy/Axtle/Pemrydi (pemetrexed) products. Authorization must be supported by one of the following: FDA-approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer‑reviewed literature that meets CMS standards (see documentation requirements). Continuation requests for a previously authorized, not-approvable medication may be exempt when the member has not progressed on therapy, the medication was used within the last year without a lapse >30 days, and no additional agents are being added to the request.

Applies to all pemetrexed products (Alimta, Pemfexy, Axtle, Pemrydi)
Prior authorization must be obtained before reimbursement will be considered

Denial Risk

Triggers for Denial

Requests will be denied when any of the exclusion criteria are met, including dosing above single‑dose limit, unsupported indications, disease progression, or use in histologies not supported by evidence.

Line of Therapy Criteria

first-line

First-line MPM: Use of pemetrexed-containing regimens as first-line therapy for malignant pleural mesothelioma (single agent or in combination with platinum with or without bevacizumab), including combination with platinum for operable stage I‑IIIA disease and combination with pembrolizumab plus platinum for unresectable/metastatic disease.

See MPM covered indications; J9304 (Pemfexy) not supported for MPM.

first-line

First-line NSCLC: Use of pemetrexed-containing regimens as first-line therapy for recurrent or metastatic non-squamous NSCLC in combination with carboplatin or cisplatin; first-line with carboplatin/cisplatin plus pembrolizumab for EGFR‑negative and ALK‑negative disease; first-line with amivantamab plus carboplatin for EGFR exon 20 insertion mutations; or first-line durvalumab + tremelimumab + platinum chemotherapy for EGFR‑ and ALK‑negative disease (may be followed by maintenance durvalumab ± pemetrexed).

Refer to NSCLC covered indications for additional sequencing and maintenance options; some regimens are explicitly not supported per policy.

Biomarkers and Molecular Requirements

inv-16: EGFR — Exon 20 insertion; exon 19 deletion; exon 21 L858R

EGFR alterations specifiedExon 20 insertion; exon 19 deletion; exon 21 L858R

Use contextSelection of amivantamab + carboplatin combinations and certain subsequent therapy choices in NSCLC

DocumentationEGFR mutation status must be established to support regimen selection

inv-17: ALK — Negative (for some first-line pembrolizumab combinations)

ALK status requiredNegative

Clinical relevanceRequired for selection of some first-line pembrolizumab-containing combinations in NSCLC

Definitions and Key Terms

inv-12: Vitamin supplementation — Prophylactic folic acid and vitamin B12 supplements

Supplementation recommendedProphylactic folic acid and vitamin B12 supplements

PurposeReduce hematologic toxicity, febrile neutropenia, and infection associated with pemetrexed

Clinical risk without supplementsHigher risk for severe myelosuppression in patients who did not receive vitamin supplementation

inv-13: Non-squamous NSCLC — Non-squamous histology of NSCLC where pemetrexed is indicated

DefinitionNon-squamous histology of NSCLC where pemetrexed is indicated

Covered settingsFirst-line or subsequent therapy in combination with platinum agents; maintenance single-agent pemetrexed after response/stable disease

Background

Pemetrexed is an antifolate chemotherapeutic agent used primarily in malignant pleural mesothelioma and non‑squamous non‑small cell lung cancer (NSCLC). Use requires attention to known hematologic toxicity and standard risk‑mitigation measures; prophylactic supplementation with folic acid and vitamin B12 is recommended to reduce the risk of severe myelosuppression.