ALIMTA, Pemetrexed Disodium Form

Pemetrexed (Alimta®, Pemfexy®) is an antifolate antineoplastic agent. FDA Approved Indication(s) Alimta and Pemfexy are indicated: • In combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. In combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC. • • As a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. • As a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy. Limitations of Use: Alimta and Pemfexy are not indicated for the treatment of patients with squamous cell, NSCLC. Initial treatment, in combination with cisplatin, of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.
• Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Alimta and Pemfexy are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-Small Cell Lung Cancer or Mesothelioma (must meet all):

1. Diagnosis of one of the following (a or b): a. Non-squamous NSCLC; b. One of the following malignant mesotheliomas (i, ii, iii, or iv): i. Pleural; ii. Peritoneal (off-label); iii. Pericardial (off-label); iv. Tunica vaginalis testis (off-label); Page 1 of 8

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   Pemetrexed

2. Prescribed by or in consultation with an oncologist;
   
   3. Age ≥ 18 years;
   4. If Alimta or Pemfexy is requested, member must use generic pemetrexed, unless contraindicated or clinically significant adverse effects are experienced;
3. Request meets one of the following (a or b): a. Dose does not exceed 500 mg per m2 every 21 days;
   b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.
   Approval duration: 6 months B. Thymoma or Thymic Carcinoma (off-label) (must meet all):
4. Diagnosis of thymoma or thymic carcinoma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. One of the following (a or b):
      a. Prescribed as second-line therapy (initial treatment may include surgery, radiation therapy, chemotherapy); b. Member unable to tolerate first-line combination regimens;
5. Prescribed as a single agent;
   6. If Alimta or Pemfexy is requested, member must use generic pemetrexed, unless contraindicated or clinically significant adverse effects are experienced;
6. 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).Prescribed regimen must be FDA-approved or recommended by NCCN.
   Approval duration: 6 months C. Ovarian/Fallopian Tube/Primary Peritoneal Cancer (off-label) (must meet all):
7. 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 a single agent;
   6. If Alimta or Pemfexy is requested, member must use generic pemetrexed, unless contraindicated or clinically significant adverse effects are experienced;
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).Prescribed regimen must be FDA-approved or recommended by NCCN.
   Approval duration: 6 months D. Central Nervous System Lymphoma (off-label) (must meet all):
9. Diagnosis of one of the following (a or b):
   a. Primary central nervous system (CNS) lymphoma; b. Leptomeningeal metastases;

10. Prescribed by or in consultation with an oncologist or hematologist; Page 2 of 8

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11. Age ≥ 18 years;
    4. For primary CNS lymphoma, prescribed as a single agent for one of the following (a or b): a. Relapsed or refractory disease; b. Induction therapy if member is unsuitable for or intolerant to high-dose methotrexate;
12. If Alimta or Pemfexy is requested, member must use generic pemetrexed, unless contraindicated or clinically significant adverse effects are experienced;
13. 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).Prescribed regimen must be FDA-approved or recommended by NCCN.
    Approval duration: 6 months
    E. Cervical Cancer (off-label) (must meet all):
14. Diagnosis of cervical cancer;
    
    2. Prescribed by or in consultation with an oncologist or hematologist;
    3. Age ≥ 18 years;
    4. Prescribed as a single agent as second-line or subsequent therapy;
    5. If Alimta or Pemfexy is requested, member must use generic pemetrexed, unless contraindicated or clinically significant adverse effects are experienced;
15. 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).Prescribed regimen must be FDA-approved or recommended by NCCN.
    Approval duration: 6 months F. Other diagnoses/indications (must meet 1 or 2):

16. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
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    Pemetrexed II. Continued Therapy A. All Indications in Section I (must meet all):

17. Currently receiving medication via Centene benefit or documentation supports that member has received Alimta or Pemfexy for a covered indication and has had at least one dose in the last 90 days;
18. Member is responding positively to therapy;
    3. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 500 mg/m2 every 21 days;
       b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.
       Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

19. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
       III. Diagnoses/Indications for which coverage is NOT authorized:
       A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALK: anaplastic lymphoma kinase CNS: central nervous system EGFR: epidermal growth factor receptor FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
       Not applicable NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer Page 4 of 8

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    Pemetrexed Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of severe hypersensitivity reaction to pemetrexed • Boxed warning(s): none reported V. Dosage and Administration
    Indication NSCLC Malignant pleural mesothelioma Dosing Regimen 500 mg/m2 IV on Day 1 of each 21-day cycle as a single agent or in combination with cisplatin, or platinum therapy and pembrolizumab 500 mg/m2 IV on Day 1 of each 21-day cycle in combination with cisplatin Maximum Dose 500 mg/m2 IV infusion every 21 days VI. Product Availability
    Drug Name Alimta Pemfexy Availability Single-dose vials for injection: 100 mg, 500 mg Multi-dose vial for injection: 500 mg/20 mL VII.