Health Net pemetrexed Coverage Policy Update

Coverage Criteria for Pemetrexed (Alimta, Pemfexy, Axtle)

Initial Approval Criteria (Non-Small Cell Cancer or Mesothelioma)

Covered when ALL of the following are met for Initial Approval (Non‑Small Cell Cancer or Mesothelioma):

Initial Approval - NSCLC/Mesothelioma: 1. Diagnosis: non-squamous non-small cell lung cancer (NSCLC) or malignant mesothelioma (including pleural; peritoneal, pericardial, tunica vaginalis testis as listed). 2. Prescribed by or in consultation with an oncologist. 3. Age ≥ 18 years. 4. Request meets one of the allowed uses: FDA-approved indication or NCCN/guideline-supported off-label use. 5. If Alimta, Pemfexy, or Axtle is requested, member must use generic pemetrexed unless contraindicated or clinically significant adverse effects. 6. Dose does not exceed 500 mg every 21 days. 7. Prescribed regimen must be FDA-approved or recommended by NCCN; for off-label uses the dose/regimen must be supported by practice guidelines or peer-reviewed literature and prescriber must submit supporting evidence.

Approval duration: Commercial 6 months or to member renewal date; Medicaid/HIM 6 months.

Thymoma / Thymic Carcinoma (off-label)

Covered when ALL of the following are met for Thymoma or Thymic Carcinoma (off-label):

Thymoma/Thymic Carcinoma: 1. Diagnosis of thymoma or thymic carcinoma. 2. Prescribed by or in consultation with an oncologist. 3. Age > 18 years. 4. Prescribed as second-line therapy (initial treatment may include surgery, radiation, or chemotherapy). 5. Member unable to tolerate first-line combination regimens. 6. Prescribed as single-agent pemetrexed. 7. If Alimta, Pemfexy, or Axtle is requested, member must use generic pemetrexed unless contraindicated or clinically significant adverse effects. 8. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

Approval duration: Commercial 6 months or to member renewal; Medicaid/HIM 6 months.

Ovarian/Fallopian Tube/Primary Peritoneal Cancer (off-label)

Covered when ALL of the following are met for Ovarian/Fallopian Tube/Primary Peritoneal Cancer (off-label):

Ovarian/Fallopian Tube/Primary Peritoneal: 1. Diagnosis of ovarian, fallopian tube, or primary peritoneal cancer. 2. Prescribed by or in consultation with an oncologist. 3. Age > 18 years. 4. Disease is persistent or recurrent. 5. Prescribed as single-agent pemetrexed. 6. If Alimta, Pemfexy, or Axtle is requested, member must use generic pemetrexed unless contraindicated or clinically significant adverse effects. 7. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence). 8. Prescribed regimen must be FDA-approved or recommended by NCCN.

Approval duration: Medicaid/HIM 6 months; Commercial 6 months or to member renewal.

Central Nervous System Lymphoma (off-label)

Covered when ALL of the following are met for Central Nervous System Lymphoma (off-label):

CNS Lymphoma: 1. Diagnosis: primary central nervous system (CNS) lymphoma or leptomeningeal metastases. 2. Age ≥ 18 years. 3. Prescribed by or in consultation with an oncologist or hematologist. 4. For primary CNS lymphoma: prescribed as single agent for relapsed/refractory disease, or as induction therapy if unsuitable or intolerant to high‑dose methotrexate. 5. If Alimta, Pemfexy, or Axtle is requested, member must use generic pemetrexed unless contraindicated or clinically significant adverse effects. 6. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence). 7. Prescribed regimen must be FDA-approved or recommended by NCCN.

Approval duration: Commercial 6 months or to member renewal; Medicaid/HIM 6 months.

Cervical or Vaginal Cancer (off-label)

Covered when ALL of the following are met for Cervical or Vaginal Cancer (off-label):

Cervical/Vaginal Cancer: 1. Diagnosis of cervical cancer or vaginal cancer. 2. Prescribed by or in consultation with an oncologist. 3. Age > 18 years. 4. Prescribed as a single agent as second-line or subsequent therapy. 5. If Alimta, Pemfexy, or Axtle is requested, member must use generic pemetrexed unless contraindicated or clinically significant adverse effects. 6. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence). 7. Prescribed regimen must be FDA-approved or recommended by NCCN.

Approval duration: Commercial 6 months or to member renewal; Medicaid/HIM 6 months.

Non‑Nasopharyngeal Cancer (off-label)

Covered when ALL of the following are met for Non‑Nasopharyngeal Cancer (off-label):

Non-Nasopharyngeal Cancer: 1. Diagnosis of non‑nasopharyngeal cancer. 2. Prescribed by or in consultation with an oncologist. 3. Age ≥ 18 years. 4. If Alimta, Pemfexy, or Axtle is requested, member must use generic pemetrexed unless contraindicated or clinically significant adverse effects. 5. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence). 6. Prescribed regimen must be FDA-approved or recommended by NCCN.

Approval duration: Commercial 6 months or to member renewal; Medicaid/HIM 6 months.

Continued Therapy Criteria

Covered when ALL of the following are met for Continued Therapy:

Continued Therapy: 1. Member is currently receiving pemetrexed via the Centene benefit or documentation supports that the member has received Alimta, Pemfexy, or Axtle for a covered indication for at least 30 days. 2. All indications in Section I are met. 3. Member is responding positively to therapy. 4. New dose does not exceed 500 mg every 21 days. 5. If a dose increase is requested, the new dose must be supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence). 6. Prescribed regimen must be FDA-approved or recommended by NCCN.

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to member renewal date.

General Dosing/Administration Criteria

Coverage is provided when the indications and administration align with FDA labeling and referenced NCCN-supported uses; see specific criteria in other policy sections.

Dosing and administration: Pemetrexed dosing for NSCLC and malignant pleural mesothelioma: 500 mg/m2 IV on Day 1 of each 21‑day cycle; may be given as single agent or in combination with cisplatin/platinum. Pemfexy (per updated prescribing information) is indicated for use in combination with pembrolizumab and platinum chemotherapy for initial treatment of metastatic non‑squamous NSCLC in patients without EGFR or ALK genomic tumor aberrations.500 mg IV q21 days

See Appendix/Product Availability for vial strengths.

Non‑FDA approved indications for pemetrexed that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the referenced off‑label use policies.

Use of pemetrexed for off‑label indications requires support per the plan’s off‑label use requirements. Providers must follow the referenced off‑label policies (for example, HIM.PA.154 for Marketplace and CP.PMN.53 for Medicaid) and submit clinical evidence or guideline support to justify the requested off‑label use.

Requests for non‑FDA approved indications that lack sufficient documentation as required by the off‑label use policies may be determined to be not medically necessary and denied. Providers should include relevant peer‑reviewed literature, guideline recommendations, or other evidence per the referenced policies when seeking authorization for off‑label uses.

Covered Regimens and Indications

Regimen	Indication	Coverage
Pemetrexed in combination with cisplatin
Initial treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
Covered when criteria met per policy (see Initial Approval Criteria)
Pemetrexed in combination with cisplatin
Initial treatment of patients with unresectable malignant pleural mesothelioma
Covered when criteria met per policy (see Initial Approval Criteria)
Pemetrexed as single-agent maintenance
Maintenance treatment for locally advanced or metastatic non-squamous NSCLC after platinum-based first-line chemotherapy
Covered when criteria met per policy (see Initial Approval Criteria)
Pemetrexed in combination with pembrolizumab and platinum chemotherapy (Alimta and Pemfexy only)
Initial treatment of metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations
Covered when criteria met per policy and per updated Pemfexy prescribing information

Dose	Regimen Notes	Coverage
Pemetrexed 500 mg/m2 IV on Day 1 of each 21-day cycle
Can be administered as single agent or in combination with platinum chemotherapy; Pemfexy labeling updated to include combination with pembrolizumab and platinum for NSCLC without EGFR/ALK mutations
covered

Dose	Combination Agent	Indication/Coverage
Pemetrexed 500 mg/m2 IV on Day 1 of each 21-day cycle
Cisplatin
Combination with cisplatin for malignant pleural mesothelioma (unresectable or not candidates for curative surgery) — covered when criteria met

Line of Therapy Specifications

first-line | second-line

Line of therapy notes: FDA-approved uses include initial treatment (with cisplatin) for non-squamous NSCLC and malignant pleural mesothelioma; single‑agent maintenance for non-squamous NSCLC after platinum‑based first‑line chemotherapy; and initial combination with pembrolizumab and platinum chemotherapy for metastatic non‑squamous NSCLC in patients without EGFR or ALK genomic tumor aberrations. Off‑label uses in this policy are generally for second‑line or subsequent therapy as specified per indication.

first-line | second-line

Line of therapy notes: Policy includes first‑line and later‑line uses as described by FDA labeling and NCCN; thymoma/thymic carcinoma single‑agent option is provided for members who cannot tolerate first‑line combination regimens per NCCN. Continued therapy language updated to require at least 30 days of prior therapy for renewal consideration.

Biomarker and Test Requirements

inv-28: EGFR / ALK — key biomarker requirement nodes (leaf-level)

EGFR statusNSCLC must have no EGFR genomic tumor aberrations for pemfexy combination with pembrolizumab and platinum chemotherapy

ALK statusNSCLC must have no ALK genomic tumor aberrations for pemfexy combination with pembrolizumab and platinum chemotherapy

Biomarker requirement summaryFor metastatic non‑squamous NSCLC treated with pemfexy + pembrolizumab + platinum, tumors must be negative for EGFR and ALK mutations per updated prescribing information

inv-29: EGFR, ALK — NSCLC must be without EGFR or ALK gene mutation per updated Pemfexy prescribing information

Updated Pemfexy prescribing informationPemfexy indicated in combination with pembrolizumab and platinum chemotherapy for initial treatment of metastatic non‑squamous NSCLC with no EGFR or ALK genomic tumor aberrations

HCPCS/J-Codes and Dosing Limits

HCPCS/J-code group for pemetrexed productsHCPCS

J9304	Injection,pemetrexed (pemfexy) 10 mg.
J9305	Injection,pemetrexed,not otherwise specified,_l0 mg.
J9314	Injection,pemetrexed not therapeutically equivalent to J9305, 10 mg.
J9292	Injection, pemetrexed (avyxa), not therapeutically equivalent to J9305, 10 mg.
J9294	.
J9296	Injection,pemetrexed accord) not therapeutically equivalent to J9305,10 mg_.
J9297	Injection_pemetrexed_ sandoz)_not therapeutically equivalent to J9305,10 mg.
J9322	Injection,pemetrexed (bluepoint) not therapeutically equivalent to J9305,10 mg.
J9323	Injection,pemetrexed ditromethamine; 10mg_.
J9324	Injection,pemetrexed (pemrydi rtu)10 mg_.

inv-13: Maximum dose per administration — policy maximum dose (≤ 500 mg every 21 days)

Policy maximum dose per administrationDose must not exceed 500 mg every 21 days

Continued therapy limitNew or continued doses must not exceed 500 mg every 21 days unless supported by guidelines or literature

Specificity for indicationsMaximum 500 mg/21 days applies to NSCLC and malignant pleural mesothelioma dosing statements in the policy

inv-14: Dosing frequency — common dosing frequency (500 mg IV every 21 days)

Common dosing frequency500 mg IV on Day 1 of each 21‑day cycle (500 mg IV every 21 days)

Regimen contextsCan be given as single agent or in combination with cisplatin/platinum; Alimta and Pemfexy may be combined with pembrolizumab and platinum for eligible NSCLC

Provider Actions, Documentation & Billing Guidance

Prior Authorization

Prior Authorization Required

Prior authorization is required. Providers must obtain prior authorization and demonstrate the member meets the clinical indication(s) and all criteria in this policy prior to initiation of therapy.

Prior authorization required per this clinical policy.
Requests for non‑FDA approved (off‑label) indications addressed in this policy may be considered if sufficient supporting evidence is provided; otherwise they may be denied.
Requests lacking required clinical documentation (see below) may be denied or returned for more information.

Documentation Required

Required Clinical Documentation

Providers must submit documentation supporting that the member has met all approval criteria.

Required clinical documentation includes: office chart notes, relevant diagnostic and laboratory results, pathology reports, imaging, prior therapy history, and any supporting peer‑reviewed literature or practice guideline citations for off‑label uses.

Background and Drug Information

Pemetrexed is an antifolate antineoplastic agent with FDA‑approved indications for use in combination with cisplatin for the initial treatment of locally advanced or metastatic non‑squamous non‑small cell lung cancer and for unresectable malignant pleural mesothelioma, and as single‑agent maintenance or treatment for non‑squamous NSCLC. Off‑label uses may be considered when supported by practice guidelines or peer‑reviewed literature and when documentation is provided per the off‑label use policies referenced in this policy.

Definitions and Abbreviations

inv-24: NSCLC — definition / abbreviation included in Appendix A

AbbreviationNSCLC = non-small cell cancer lung

Appendix locationAbbreviation provided in Appendix A of the policy document

Related abbreviationsAppendix A also defines ALK and EGFR relevant to NSCLC biomarker requirements

inv-25: non-small cell lung cancer — NSCLC abbreviation mapping

Term mappingnon-small cell lung cancer = NSCLC

UsagePolicy uses 'NSCLC' abbreviation throughout clinical and dosing sections as defined in Appendix A

Context

Policy Revision History and Changes

2025-01-01 (1Q 2025 annual review)policy_updateLatest

Added Commercial line of business; removed hematologist as prescriber option for cervical cancer; added off-label indications for vaginal cancer and non‑nasopharyngeal cancers per NCCN; revised continued therapy language to require at least 30 days of prior pemetrexed; updated HCPCS code descriptions for J9297 and J9323; added newly approved product Axtle.

2024-11-06coding_update

Added HCPCS code J9292 to the policy.

2023-10-26

OpenPayer

Pemetrexed (Alimta, Pemfexy, Axtle) coverage

Coverage Criteria for Pemetrexed (Alimta, Pemfexy, Axtle)

Covered Regimens and Indications

Line of Therapy Specifications

Biomarker and Test Requirements

HCPCS/J-Codes and Dosing Limits

Provider Actions, Documentation & Billing Guidance

Background and Drug Information

Definitions and Abbreviations

Policy Revision History and Changes