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    v1.0.31
    OpenPayerPolicy UpdatesHematology/OncologyBCBS Tennessee Pemetrexed Prior Auth | OpenPayer
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    CurrentBlue Cross Blue Shield of TennesseePolicy ID_CHS_19002025_1026

    Pemetrexed Coverage

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    Coverage and prior authorization for pemetrexed products used for specified FDA-approved and compendial oncology indications when the applicable disease, regimen, and approval criteria are met.

    Policy Summary
    PayerBlue Cross Blue Shield of Tennessee
    PolicyPemetrexed Coverage
    Policy CodePolicy ID_CHS_19002025_1026
    Change TypeNo material clinical or coverage changes
    Effective DateDecember 31, 2026
    Next Review DateN/A
    Key ActionSubmit documentation of the cancer diagnosis, disease status, prior treatment or progression when applicable, the requested pemetrexed regimen, and required combination therapy.
    SourceLink
    POLICY UPDATE CHANGES

    No material clinical or coverage changes in this revision.

    6 monthsStandard authorization period
    2FDA-approved disease groups
    9Compendial disease groups
    Squamous NSCLCExplicit coverage exclusion
    24 months

    OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.

    Maximum pembrolizumab combination duration
    500 mg/m² q21dCommon maximum dosing regimen

    Covered Indications and Exclusions

    Bladder cancer

    Authorization of 6 months may be granted when the indication and treatment setting are met.

    Bladder cancer: Locally advanced, metastatic, or relapsed transitional cell urothelium cancer treated with pemetrexed as second-line treatment.

    Pleural or peritoneal mesothelioma

    Authorization of 6 months may be granted when any one of the following regimen criteria is met.

    Pleural or peritoneal mesothelioma regimen

    • Single-agent or platinum combination: The requested medication will be used as a single agent or in combination with cisplatin or carboplatin.
    • Bevacizumab or durvalumab regimen: The requested medication will be used in combination with bevacizumab or durvalumab (Imfinzi) and either cisplatin or carboplatin.
    • First-line pembrolizumab regimen: The requested medication will be used as first-line therapy in combination with pembrolizumab and platinum chemotherapy.First-line

    Non-small cell lung cancer

    Authorization of 6 months may be granted.

    Non-squamous NSCLC: Treatment of non-squamous non-small cell lung cancer, including leptomeningeal metastases.

    Squamous histology is excluded.

    Ovarian, fallopian tube, and primary peritoneal cancer

    Authorization of 6 months may be granted.

    Persistent or recurrent gynecologic cancer: Treatment of persistent or recurrent epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, carcinosarcoma (malignant mixed Müllerian tumors), clear cell carcinoma of the ovary, grade 1 endometrioid carcinoma, low-grade serous carcinoma or ovarian borderline epithelial tumor (low malignant potential), or mucinous carcinoma of the ovary, as single-agent therapy.Persistent or recurrent disease

    Single-agent therapy required.

    Primary CNS lymphoma

    Authorization of 6 months may be granted.

    Primary CNS lymphoma: Treatment of primary central nervous system lymphoma as a single agent.

    Single-agent therapy required.

    Thyroid cancer

    Authorization of 6 months may be granted when all criteria for the applicable thyroid carcinoma subtype are met.

    Thyroid carcinoma subtype criteria

    • Papillary or follicular thyroid carcinoma: Disease is unresectable or metastatic; disease is not amenable to radioactive iodine therapy; and the requested medication will be used in combination with carboplatin.
    • Oncocytic/Hürthle cell thyroid carcinoma: Disease is unresectable or metastatic and the requested medication will be used in combination with carboplatin.
    • Anaplastic thyroid carcinoma: Disease is metastatic and the requested medication will be used in combination with carboplatin after disease progression following prior treatment.After disease progression following prior treatment

    Thymomas and thymic carcinomas

    Authorization of 6 months may be granted.

    Thymoma or thymic carcinoma: Treatment of thymoma or thymic carcinoma as a single agent.

    Single-agent therapy required.

    FDA-approved indications

    FDA-approved indications are covered when all approval criteria are met and the member has no exclusions to the prescribed therapy.

    • Metastatic non-squamous NSCLC initial treatment: In combination with pembrolizumab and platinum chemotherapy for initial treatment of metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations.No EGFR or ALK genomic tumor aberrations
    • Locally advanced or metastatic non-squamous NSCLC initial treatment: In combination with cisplatin for initial treatment of locally advanced or metastatic non-squamous NSCLC.Initial treatment
    • Non-squamous NSCLC maintenance: As a single agent for maintenance treatment of locally advanced or metastatic non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.No progression after 4 cycles

    Compendial uses

    The following compendial uses are covered when all approval criteria are met; all other indications are experimental/investigational and not medically necessary.

    Compendial uses: Bladder cancer; pleural, peritoneal, pericardial, or tunica vaginalis testis mesothelioma; nonsquamous NSCLC; ovarian, fallopian tube, or primary peritoneal cancer; primary CNS lymphoma; thyroid carcinoma; thymomas and thymic carcinomas; cervical cancer; or vaginal cancer.

    Specific treatment criteria apply to the listed uses. All other indications are experimental/investigational and not medically necessary.

    Oncocytic/Hürthle cell thyroid carcinoma

    Covered for progressive and/or symptomatic oncocytic/Hürthle cell thyroid carcinoma when all criteria are met.

    Oncocytic/Hürthle cell thyroid carcinoma: The disease is progressive and/or symptomatic; the disease is unresectable or metastatic; and pemetrexed is used in combination with carboplatin.

    Authorization period is 6 months.

    Anaplastic carcinoma

    Covered for anaplastic carcinoma when all criteria are met.

    Anaplastic carcinoma: The disease is metastatic and pemetrexed is used in combination with carboplatin after disease progression following prior treatment.

    Authorization period is 6 months.

    Thymoma or thymic carcinoma

    Covered when the requested therapy is used as a single agent.

    Thymic malignancy: Diagnosis is thymoma or thymic carcinoma and pemetrexed is used as a single agent.

    Authorization period is 6 months.

    Cervical cancer

    Covered for persistent, recurrent, or metastatic disease.

    Cervical cancer: Diagnosis is persistent, recurrent, or metastatic cervical cancer.

    Authorization period is 6 months.

    Vaginal cancer

    Covered for subsequent treatment when used as a single agent.

    Vaginal cancer: Diagnosis is recurrent or metastatic vaginal cancer, pemetrexed is being used as subsequent treatment, and pemetrexed is used as a single agent.

    Authorization period is 6 months.

    Continuation therapy

    Continuation is covered when all continuation criteria are met.

    Continuation therapy: The member is requesting reauthorization for an indication listed in the coverage criteria; there is no evidence of unacceptable toxicity; and there is no evidence of disease progression while on the current regimen.

    Authorization is for 6 months. Use with pembrolizumab for pleural or peritoneal mesothelioma, including pericardial mesothelioma and tunica vaginalis testis mesothelioma, is limited to 24 months total.

    Pemetrexed is not indicated for squamous cell non-small cell lung cancer (NSCLC); coverage will not be provided for members with this histology.

    Indications other than the specified FDA-approved and compendial uses are considered experimental/investigational and not medically necessary.

    Quantity Limits and Dosing Regimens

    Maximum dosing regimen
    Bladder cancerIntravenous 500 mg/m² every 21 days
    Malignant pleural, peritoneal, pericardial, or tunica vaginalis testis mesotheliomaIntravenous 500 mg/m² every 21 days
    Non-small cell lung cancer (NSCLC)Intravenous 500 mg/m² every 21 days
    Maximum dosing regimen
    Cervical cancerIntravenous 900 mg/m² every 21 days
    Ovarian cancerIntravenous 900 mg/m² every 21 days
    Fallopian tube or primary peritoneal cancer

    Authorization, Documentation, and Denial Risks

    Prior Authorization

    Obtain prior authorization before treatment

    Prior authorization is required for the listed pemetrexed indications. Authorization may generally be granted for 6 months when the applicable disease, treatment setting, regimen, and clinical criteria are met.

    Prior Authorization

    Track authorization and continuation periods

    Initial authorization is generally granted for 6 months under the indication-specific criteria. Continuation authorization is also generally granted for 6 months when continuation criteria are met; use with pembrolizumab for specified mesothelioma is limited to 24 months total.

    • For reauthorization, there must be no unacceptable toxicity or disease progression on the current regimen.
    • For mesothelioma treated with pembrolizumab, total authorization may be limited to 24 months.

    Therapeutic Context

    Pemetrexed is an antineoplastic agent used in combination regimens and as single-agent therapy across selected thoracic, mesothelial, gynecologic, hematologic, and other malignancies. Coverage distinguishes FDA-approved uses from specified compendial uses and excludes squamous NSCLC; eligibility depends on the tumor type, disease extent or progression, treatment line, and accompanying agents when specified.

    Recognized Off-Label Use

    Recognized off-label indication
    Drug statusThe use must involve an FDA-approved drug
    Recognized referenceThe off-label use must be recognized in a statutorily recognized standard reference compendium
    Published evidenceThe off-label use may be supported by published peer-reviewed medical literature
    Tennessee requirementCoverage complies with Tennessee Code Annotated Section 56-7-2352

    Treatment-Line Requirements

    Second-line therapy

    Second-line therapy applies when the following criterion is met.

    Second-line bladder cancer: Locally advanced, metastatic, or relapsed transitional cell urothelium cancer is treated with pemetrexed as second-line treatment.Second-line

    First-line therapy

    First-line therapy applies when the following criterion is met.

    Initial or first-line FDA-approved therapy: Initial treatment of metastatic or locally advanced non-squamous NSCLC, initial treatment of unresectable or non-curable malignant pleural mesothelioma, or first-line pembrolizumab/platinum therapy for specified mesothelioma.Initial or first-line

    Molecular Eligibility

    Biomarker requirement
    EGFR aberrationsNo EGFR genomic tumor aberrations may be present
    ALK aberrationsNo ALK genomic tumor aberrations may be present
    Applicable treatmentThe requirement applies to initial treatment of metastatic non-squamous NSCLC with pembrolizumab and platinum chemotherapy

    Indication-Specific Treatment Regimens

    RegimenCovered indicationCoverage
    Pemetrexed plus pembrolizumab and platinum chemotherapyInitial treatment of metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrationsCovered
    RegimenCovered indicationCoverage
    Pemetrexed plus cisplatinInitial treatment of locally advanced or metastatic non-squamous NSCLCCovered
    RegimenCovered indicationCoverage
    Pemetrexed single agent after four cycles of platinum-based first-line chemotherapy without progressionMaintenance treatment of locally advanced or metastatic non-squamous NSCLCCovered
    RegimenCovered indicationCoverage
    Pemetrexed single agentRecurrent metastatic non-squamous NSCLC after prior chemotherapyCovered
    RegimenCovered indicationCoverage
    Pemetrexed plus cisplatinInitial treatment of unresectable malignant pleural mesothelioma or disease in a patient otherwise not a candidate for curative surgeryCovered
    RegimenCovered indicationCoverage
    Pemetrexed single agent; or pemetrexed plus cisplatin or carboplatin; or pemetrexed plus bevacizumab or durvalumab and cisplatin or carboplatin; or first-line pemetrexed plus pembrolizumab and platinum chemotherapyPleural, peritoneal, pericardial, or tunica vaginalis testis mesotheliomaCovered
    RegimenCovered indicationCoverage
    Pemetrexed single agentPersistent or recurrent specified epithelial ovarian, fallopian tube, or primary peritoneal cancers, including specified carcinosarcoma, clear cell, grade 1 endometrioid, low-grade serous or borderline epithelial, and mucinous ovarian cancersCovered
    RegimenCovered indicationCoverage
    Pemetrexed single agentPrimary CNS lymphoma; thymoma or thymic carcinomaCovered
    RegimenCovered indicationCoverage
    Pemetrexed plus carboplatinProgressive and/or symptomatic papillary, follicular, oncocytic/Hürthle cell, or anaplastic thyroid carcinoma meeting applicable subtype criteriaCovered
    RegimenCovered indicationCoverage
    Pemetrexed plus carboplatinProgressive and/or symptomatic oncocytic/Hürthle cell thyroid carcinoma that is unresectable or metastaticCovered
    RegimenCovered indicationCoverage
    Pemetrexed plus carboplatinMetastatic anaplastic thyroid carcinoma after disease progression following prior treatmentCovered
    RegimenCovered indicationCoverage
    Pemetrexed as a single agentThymoma or thymic carcinomaCovered
    RegimenCovered indicationCoverage
    Pemetrexed as subsequent treatment and as a single agentRecurrent or metastatic vaginal cancerCovered
    RegimenCovered indicationCoverage
    Pemetrexed with pembrolizumabPleural, peritoneal, pericardial, or tunica vaginalis testis mesothelioma treated with pembrolizumab; total use may be authorized for up to 24 monthsCovered
    Policy Summary
    PayerBlue Cross Blue Shield of Tennessee
    PolicyPemetrexed Coverage
    Policy CodePolicy ID_CHS_19002025_1026
    Change TypeNo material clinical or coverage changes
    Effective DateDecember 31, 2026
    Next Review DateN/A
    Key ActionSubmit documentation of the cancer diagnosis, disease status, prior treatment or progression when applicable, the requested pemetrexed regimen, and required combination therapy.
    SourceLink
    On This Page
    Covered Indications and ExclusionsQuantity Limits and Dosing RegimensAuthorization, Documentation, and Denial RisksTherapeutic ContextRecognized Off-Label UseTreatment-Line RequirementsMolecular EligibilityIndication-Specific Treatment Regimens
  1. Recurrent metastatic non-squamous NSCLC: As a single agent for treatment of recurrent, metastatic non-squamous NSCLC after prior chemotherapy.After prior chemotherapy
  2. Malignant pleural mesothelioma: In combination with cisplatin for initial treatment of malignant pleural mesothelioma when disease is unresectable or the patient is otherwise not a candidate for curative surgery.Initial treatment
    3. Intravenous 900 mg/m² every 21 days
    Indication-specific maximum dosing
    Thyroid carcinoma, including papillary, follicular, oncocytic, and anaplastic carcinomasIntravenous 500 mg/m² every 21 days
    Papillary and follicular thyroid carcinomaIntravenous 500 mg/m² every 21 days
    Oncocytic/Hürthle cell and anaplastic thyroid carcinomaIntravenous 500 mg/m² every 21 days
    Vaginal cancerIntravenous 900 mg/m² every 21 days
    Quantity-limit table regimens
    Primary CNS lymphomaIntravenous 900 mg/m² every 14 days
    Primary CNS lymphomaIntravenous 500 mg/m² every 21 days
    Thymoma or thymic carcinomaIntravenous 900 mg/m² every 14 days
    Thymoma or thymic carcinomaIntravenous 500 mg/m² every 21 days
    Documentation Required

    Submit complete clinical documentation

    Submit documentation of the cancer diagnosis, disease status, prior treatment or progression when applicable, the requested pemetrexed regimen and combination therapy. For reauthorization, document clinical benefit without unacceptable toxicity or disease progression.

    • Document the applicable disease status, such as unresectable, metastatic, persistent, recurrent, or progressive disease when required.
    • Identify whether pemetrexed is being used as a single agent or with the required combination therapy.
    • For continuation, document the absence of unacceptable toxicity and disease progression on the current regimen.
    Denial Risk

    Confirm NSCLC is nonsquamous

    Coverage will be denied for members with squamous cell NSCLC because pemetrexed is not indicated for this histology.

    Denial Risk

    Use a listed indication

    Indications not identified as FDA-approved or listed compendial uses are considered experimental/investigational and not medically necessary. Confirm that the requested use is one of the policy’s covered FDA-approved or specified compendial indications.

    Denial Risk

    Verify all approval requirements

    The applicable indication and all approval criteria must be satisfied, and the member must have no exclusions to the prescribed therapy. Requests that do not meet these requirements are not covered under the policy.

    Denial Risk

    Address clinical criteria before requesting authorization

    Authorization may be denied when the requested indication does not meet the applicable disease-status, prior-treatment, combination-regimen, or continuation criteria. Ongoing therapy may also be denied when there is disease progression or unacceptable toxicity.

    • Confirm required disease extent or status before submitting the request.
    • Document required prior treatment or progression when applicable.
    • For continuation, document no unacceptable toxicity and no disease progression on the current regimen.
    Denial Risk

    Document thyroid disease status and carboplatin use

    For thyroid carcinoma and anaplastic carcinoma, authorization may be denied if the required disease status or carboplatin combination is not documented. Anaplastic carcinoma additionally requires metastatic disease and progression following prior treatment.

    • Papillary or follicular thyroid carcinoma: document unresectable or metastatic disease, lack of amenability to radioactive iodine therapy, and combination with carboplatin.
    • Oncocytic/Hürthle cell thyroid carcinoma: document unresectable or metastatic disease and combination with carboplatin.
    • Anaplastic carcinoma: document metastatic disease, carboplatin combination, and progression following prior treatment.

    Salvage therapy

    Salvage therapy applies when the following criterion is met.

    Maintenance or post-chemotherapy therapy: Maintenance treatment of non-squamous NSCLC after four cycles of platinum-based first-line chemotherapy without disease progression, or treatment of recurrent metastatic non-squamous NSCLC after prior chemotherapy.After 4 cycles or after prior chemotherapy

    Salvage therapy for thyroid carcinoma

    Salvage therapy applies when the following criterion is met.

    Post-progression anaplastic carcinoma therapy: For metastatic anaplastic carcinoma, pemetrexed is used with carboplatin after disease progression following prior treatment.After disease progression following prior treatment

    Second-line therapy for vaginal cancer

    Second-line therapy applies when the following criterion is met.

    Subsequent vaginal cancer treatment: For recurrent or metastatic vaginal cancer, pemetrexed is used as subsequent treatment and as a single agent.Subsequent treatment

    First-line therapy for mesothelioma continuation or combination treatment

    First-line therapy applies when the following criterion is met.

    Mesothelioma continuation or combination treatment: For a covered pleural, peritoneal, pericardial, or tunica vaginalis testis mesothelioma indication, pemetrexed may be continued with pembrolizumab or used in the specified first-line combination regimen with pembrolizumab and platinum chemotherapy.First-line or continuation

    Continuation requires no unacceptable toxicity or disease progression; total use with pembrolizumab may not exceed 24 months.