CareSource pemetrexed Coverage & Prior Auth Update

Recommended Authorization Criteria

Mesothelioma (FDA-approved)

Approve for 1 year if ALL of the following are met

Mesothelioma approval: A) Patient is ≥ 18 years of age; AND B) Patient has malignant pleural mesothelioma OR malignant peritoneal mesothelioma OR pericardial mesothelioma OR tunica vaginalis testis mesothelioma; AND C) The medication is prescribed by or in consultation with an oncologist.

Dosing: Approve up to 500 mg/m2 IV every 3 weeks.

Non-Small Cell Lung Cancer (NSCLC) — FDA and guideline-based scenarios

Approve for 1 year if ALL of the following are met

NSCLC basic: A) Patient is ≥ 18 years of age; AND B) Patient has non-squamous non-small cell lung cancer (includes adenocarcinoma, large cell, NSCLC not otherwise specified); AND C) The medication is prescribed by or in consultation with an oncologist.

NSCLC usage contexts: Patient meets ONE of the following contexts: i) The medication is used for chemoradiation, perioperative, neoadjuvant, adjuvant, or induction therapy in combination with platinum chemotherapy (e.g., cisplatin or carboplatin); OR ii) The medication is used for recurrent, advanced, or metastatic disease where one of the molecular/therapy-specific conditions below is met; OR iii) The medication is used as maintenance or subsequent therapy as single agent or in combination.

Examples of combination agents include platinum chemotherapy, immune checkpoint inhibitors (eg, pembrolizumab, nivolumab, ipilimumab).

Molecular and sequencing rules for recurrent/advanced disease: For recurrent/advanced disease: a) If tumor is negative or unknown for targetable mutations, pemetrexed may be used as initial therapy in combination regimens or as maintenance/subsequent therapy; OR b) If tumor is positive for listed genomic alterations, use is allowed in specific first-line or subsequent pathways depending on the mutation and prior receipt of targeted therapy (listed alterations include EGFR exon 19 deletion, EGFR exon 21 L858R and other specified EGFR variants, EGFR exon 20 insertion, ALK rearrangement, ROS1 rearrangement, BRAF V600E, MET exon 14 skipping, RET rearrangement, NRG1 fusion, NTRK fusion, ERBB2/HER2).

Some pathways require prior targeted therapy for that specific mutation before using pemetrexed as subsequent therapy.

Intrathecal use for leptomeningeal metastases

Approve when ALL of the following are met

Leptomeningeal metastases intrathecal: A) The medication is used intrathecally for leptomeningeal metastases; AND B) The medication is prescribed by or in consultation with an oncologist; AND C) The medication is being used for leptomeningeal disease (including if intrathecal administration has not previously been given in this setting).

Dosing: Approve up to 50 mg intrathecally with schedule: no more than twice in the first week, then no more frequently than once every 3 weeks.

Other uses with supportive evidence

Approve for 1 year if ALL of the following are met (per tumor type)

Cervical cancer: A) Patient is ≥ 18 years of age; AND B) Patient has recurrent or metastatic cervical cancer; AND C) Medication is used as subsequent therapy; AND D) The medication is prescribed by or in consultation with an oncologist.

Dosing: Approve up to 900 mg/m2 IV every 3 weeks.

Ovarian/fallopian tube/primary peritoneal cancer: A) Patient is ≥ 18 years of age; AND B) At least one other systemic chemotherapy regimen has been tried; AND C) The medication is prescribed by or in consultation with an oncologist.

Dosing: Approve up to 900 mg/m2 IV every 3 weeks.

Primary CNS lymphoma: A) Patient is ≥ 18 years of age; AND B) The medication is prescribed by or in consultation with an oncologist.

Dosing: Approve up to 900 mg/m2 IV every 3 weeks.

Pemetrexed is not indicated for squamous cell NSCLC. Requests for coverage when the diagnosis is squamous cell non–small cell lung cancer should be denied because the product labeling and this policy do not support use in that histology (see FDA-approved limitations).

In addition, coverage is not recommended for circumstances not listed in the Recommended Authorization Criteria; only indications and clinical contexts explicitly described in the criteria (mesothelioma, non-squamous NSCLC scenarios, intrathecal leptomeningeal therapy, and other listed tumor-specific supportive-evidence uses) are considered for authorization.

Coverage of pemetrexed for indications or clinical scenarios that are not listed in the Recommended Authorization Criteria is not recommended. The policy will be updated as new published data become available and may expand or restrict covered uses based on emerging evidence and guideline changes.

Providers seeking use outside the listed criteria should submit supporting clinical evidence; absent documentation meeting a listed criterion, requests are at high risk for denial per the policy’s not-recommended-for-approval guidance.

Approved Regimens and Combinations

Regimen	Indication / context	Coverage status	Supporting details
Pemetrexed + cisplatin or carboplatin
Non‑squamous non‑small cell lung cancer (NSCLC) — used for chemoradiation, perioperative, neoadjuvant, adjuvant, induction, recurrent/advanced, maintenance, or subsequent therapy per guideline placements

Policy and NCCN guidelines list pemetrexed plus a platinum agent (cisplatin or carboplatin) as an option for non‑squamous NSCLC; combinations with PD‑1/PD‑L1 inhibitors (e.g., pembrolizumab) or other immune checkpoint regimens are included in recommended regimen options.

Regimen	Indication / context	Coverage status	Supporting details
Pemetrexed + cisplatin (or carboplatin); single‑agent pemetrexed also noted
Malignant mesothelioma — induction/first‑line therapy; single‑agent pemetrexed noted for some settings

Policy approves pemetrexed with cisplatin or carboplatin for mesothelioma (FDA‑approved) as induction/first‑line therapy with dosing up to 500 mg/m2 IV no more frequently than q3w; single‑agent pemetrexed is also referenced in guideline options.

Dosing Limits and Administration

Intravenous dosing frequency and limits

Usual IV limit (many indications)Up to 500 mg/m2 IV administered no more frequently than once every 3 weeks.

Higher IV limit (supportive‑evidence indications)Up to 900 mg/m2 IV administered no more frequently than once every 3 weeks for select supportive‑evidence indications (e.g., cervical, ovarian, primary CNS lymphoma).

Thymic and vaginal cancer dosingThymic carcinoma/thymoma and vaginal cancer: approve up to 500 mg/m2 IV q3w per indication-specific criteria.

Mesothelioma dosing noteFor mesothelioma indications, approve up to 500 mg/m2 IV q3w as listed in the mesothelioma criteria.

Intrathecal dosing

Intrathecal single‑course limitApprove up to 50 mg administered intrathecally for leptomeningeal metastases.

Prior Authorization and Documentation Requirements

Prior Authorization

Prior Authorization Recommended

Prior Authorization is recommended for medical benefit coverage. Approval is recommended for patients who meet the listed criteria and dosing. Extended approvals may be allowed if the patient continues to meet criteria and dosing. Requests for doses outside the established dosing documented in this policy will be considered on a case‑by‑case basis by a clinician (e.g., Medical Director or Pharmacist). Because of the specialized skills required for evaluation, diagnosis, and monitoring of patients treated with pemetrexed, the medication must be prescribed by or in consultation with a physician who specializes in the condition being treated.

Prior authorization recommended for medical benefit coverage
Approvals provided for the duration noted in each indication
Doses outside policy dosing considered case-by-case by clinician

Prior Authorization

Prior Chemotherapy Required for Some Indications

For selected supportive‑evidence indications (for example, ovarian, fallopian tube, or primary peritoneal cancer), at least one prior systemic chemotherapy regimen must have been tried before approval is recommended.

Indication by Therapy Line

first-line

First-line contexts for NSCLC/mesothelioma: Pemetrexed may be used as initial therapy in combination with platinum chemotherapy for non-squamous NSCLC and as induction/first-line therapy in combination with cisplatin or carboplatin for mesothelioma; it may be combined with immune checkpoint inhibitors per guideline-listed combinations.

second-line

Subsequent/second-line contexts: Pemetrexed is listed for subsequent or second-line use as single agent or in combination across multiple tumor types (cervical, ovarian/fallopian tube/primary peritoneal, primary CNS lymphoma, thymic carcinoma/thymoma, vaginal cancer) depending on prior therapies and clinical context.

Genomic and Biomarker Eligibility

EGFR variants

Exon 19 deletionEGFR exon 19 deletion.

Exon 21 L858REGFR exon 21 L858R mutation.

Other specified EGFR variantsEGFR S768I, L861Q, and G719X variants.

EGFR exon 20 insertionEGFR exon 20 insertion.

Other actionable alterations

ALK rearrangementALK rearrangement (fusion).

ROS1 rearrangementROS1 rearrangement (fusion).

Key Definitions and Terms

Non-squamous NSCLC

Included non‑squamous histologiesAdenocarcinoma, large cell carcinoma, and NSCLC not otherwise specified (NOS) are considered non‑squamous.

Exclusion — squamous histologyPemetrexed is not indicated for squamous cell NSCLC; limitations of use exclude squamous NSCLC.

Clinical implicationNon‑squamous designation determines eligibility for pemetrexed in initial, maintenance, and subsequent therapy settings per guideline and FDA descriptions.

Targetable mutation negative/unknown

DefinitionTumors without identified driver genomic alterations such as EGFR, ALK, ROS1, BRAF V600E, MET exon 14 skipping, RET, NRG1, or NTRK fusions.

Clinical use implicationIf tumor is negative or mutation status is unknown, pemetrexed can be used as initial therapy in combination regimens or as maintenance/subsequent therapy per the policy.

Clinical Background

Pemetrexed is an antimetabolite chemotherapy agent used in several thoracic malignancies and other tumor types. It is FDA‑approved for malignant pleural mesothelioma (in combination with cisplatin) and for multiple non‑squamous NSCLC indications including first‑line combination with platinum chemotherapy, maintenance after platinum‑based first‑line therapy, and single‑agent therapy for recurrent or metastatic non‑squamous disease.

Clinical practice guidelines also include pemetrexed as an option in combination regimens (for example with cisplatin or carboplatin) and as maintenance or subsequent therapy in non‑squamous NSCLC; the agent is mentioned in guideline or supportive‑evidence contexts for other tumor types (for example cervical, ovarian, primary CNS lymphoma, thymic malignancies, and vaginal cancer). Dosing guidance in this policy generally limits intravenous use to ≤ 500 mg/m2 IV every 3 weeks for many indications, with higher per‑indication limits noted in select supportive‑evidence settings and a separate intrathecal dosing pathway for leptomeningeal metastases.

Policy Revision History

2025-01-22Annual revisionLatest

Expanded NSCLC molecular descriptors (added exon 21 L858R, additional EGFR variants, RET and NRG1 listings) and added intrathecal therapy option and intrathecal dosing; cervical and vaginal cancer listed as new conditions of approval.

2024-06-19Selected revision

Policy updated to remove KRAS and add NRG1 to targetable mutations, added KRAS G12C note, clarified EGFR exon 20 insertion descriptor and added RET rearrangement; added vaginal cancer as a new condition of approval.

2023-12-20

OpenPayer

Pemetrexed Products Utilization Management Medical Policy

Recommended Authorization Criteria

Approved Regimens and Combinations

Dosing Limits and Administration

Prior Authorization and Documentation Requirements

Indication by Therapy Line

Genomic and Biomarker Eligibility

Key Definitions and Terms

Clinical Background

Policy Revision History