TEMODAR, Temozolomide Form

Temozolomide (Temodar®) is an imidazotetrazine derivative. FDA Approved Indication(s) Temodar is indicated for the treatment of: • Adults with newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment. • Adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma. • Adults with refractory anaplastic astrocytoma. 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 Temodar is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Glioblastoma or Astrocytoma (must meet all):

1. Diagnosis of glioblastoma† or isocitrate dehydrogenase (IDH)-mutant astrocytoma (see Appendix D);
2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For IDH-mutant astrocytoma, disease is World Health Organization (WHO) grade 2, 3, or 4;

3. Member must use generic temozolomide, unless contraindicated or clinically significant adverse effects are experienced;

   6. Request meets one of the following (a or b): a. Dose does not exceed (i or ii): i. Glioblastoma: 75 mg/m2 per day for the first 42 consecutive days, followed by 200 mg/m2 per day on days 1-5 of each 28-day cycle; ii. IDH-mutant astrocytoma: 200 mg/m2 per day on days 1-5 of each 28-day cycle; 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 Page 1 of 8

   CLINICAL POLICY Temozolomide ___ †A high-grade WHO grade IV glioma also known as glioblastoma
   B. NCCN Compendium Supported Uses (off-label) (must meet all):

4. Prescribed for one of the following NCCN category 1 or 2a recommended indications (a - k): a. Ewing sarcoma in combination with irinotecan for relapsed or progressive disease; b. Cutaneous melanoma as subsequent therapy for metastatic or unresectable disease, or after disease progression or maximum clinical benefit from BRAF targeted therapy; c. One of the following neuroendocrine or adrenal tumors (i or ii): i. Gastrointestinal tract, pancreas, lung, thymus, or pheochromocytoma/paraganglioma; ii. Extrapulmonary poorly differentiated neuroendocrine carcinoma, large or small cell carcinoma, mixed neuroendocrine-non-neuroendocrine neoplasms;
   d. Small cell lung cancer as subsequent systemic therapy; e. Soft tissue sarcoma as palliative treatment for retroperitoneal/intra-abdominal disease, pleomorphic rhabdomyosarcoma, extremity/superficial trunk (body wall) disease, and head/neck disease; f. Nonpleomorphic rhabdomyosarcoma in combination with vincristine and irinotecan; g. Solitary fibrous tumor in combination with bevacizumab; h. Mycosis fungoides/Sézary syndrome; i. Advanced, recurrent/metastatic or inoperable uterine sarcoma, as second-line or subsequent therapy; j. Metastatic uveal melanoma; k. One of the following central nervous system cancers (i-viii): i. Pediatric diffuse high-grade gliomas (except for diffuse midline glioma, H3 K27-altered or pontine location) in patients ≥3 years, as adjuvant treatment;
   ii. Pediatric diffuse midline glioma, H3 K27-altered non-pontine location, as adjuvant treatment; iii. Oligodendroglioma (WHO grade II or III, IDH-mutant, 1p19q codeleted), as adjuvant treatment or treatment for recurrent or progressive disease; iv. Low-grade (WHO grade I) recurrent or progressive glioma;
   v. Primary CNS lymphoma;
   vi. Brain metastases; vii. Intracranial and spinal ependymoma for disease progression, as recurrent or progressive disease; viii. Medulloblastoma as a single agent for recurrence in members who received prior chemotherapy;

5. Prescribed by or in consultation with an oncologist;

   3. Age ≥ 18 years (all indications except for pediatric diffuse high-grade gliomas);
   4. Member must use generic temozolomide, unless contraindicated or clinically significant adverse effects are experienced; Page 2 of 8

   CLINICAL POLICY Temozolomide

6. Request meets one of the following (a or b): a. Dose does not exceed 200 mg/m2 per day on days 1-5 of each 28-day cycle; 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 C. Other diagnoses/indications (must meet 1 or 2):
7. 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.
      II. Continued Therapy A. All Indications in Section I (must meet all):
8. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Temodar for a covered indication and has received this medication for at least 30 days;
9. Member is responding positively to therapy;
   3. Member must use generic temozolomide, unless contraindicated or clinically significant adverse effects are experienced;
10. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 200 mg/m2 per day on days 1-5 of each 28-day cycle; 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):

11. 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 Page 3 of 8

    CLINICAL POLICY Temozolomide 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 CNS: central nervous system
       FDA: Food and Drug Administration IDH: isocitrate dehydrogenase Appendix B: Therapeutic Alternatives Not applicable
       NCCN: National Comprehensive Cancer Network RT: radiotherapy WHO: World Health Organization Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to temozolomide or any other ingredients in Temodar and dacarbazine • Boxed warning(s): none reported Appendix D: General Information • The NCCN CNS (version 2.2022) guideline no longer uses the terminology “anaplastic” to describe CNS tumors; anaplastic has been replaced with tumor specific terminology (e.g., IDH-mutant astrocytoma, IDH mutant, 1p19q codeleted oligodendroglioma). V. Dosage and Administration
       Indication Glioblastoma multiforme Dosing Regimen Concomitant phase: 75 mg/m2 daily for 42 days concomitant with focal radiotherapy (RT) (60 Gy administered in 30 fractions) followed by maintenance Temodar for 6 cycles.
       Maintenance phase: • Cycle 1: Four weeks after completing the Temodar + RT phase, Temodar is administered for an additional 6 cycles of maintenance treatment. Dosage in Cycle 1 (maintenance) is 150 mg/m2 Maximum Dose 200 mg/m2/day Page 4 of 8

    CLINICAL POLICY Temozolomide Indication Dosing Regimen Maximum Dose 200 mg/m2/day IDH-mutant astrocytoma once daily for 5 days followed by 23 days without treatment. • Cycles 2-6: At the start of Cycle 2, the dose can be escalated to 200 mg/m2. The dose remains at 200 mg/m2 per day for the first 5 days of each subsequent cycle except if toxicity occurs. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles.
    Adjuvant treatment for newly diagnosed anaplastic astrocytoma: Beginning 4 weeks after the end of RT, administer once daily for 5 consecutive days per 28-day treatment cycle for 12 cycles. Dosage of Cycle 1 is 150 mg/m2. The dose should be increased to 200 mg/m2 per day if no or minimal toxicity is experienced in Cycle 1.
    Refractory anaplastic astrocytoma: Initial dose is 150 mg/m2 once daily for 5 consecutive days per 28-day treatment cycle. The dose should be increased to 200 mg/m2 if absolute neutrophil count is ≥ 1.5 x 109/L and platelet count is ≥ 100 x 109/L. Continue Temodar until disease progression or unacceptable toxicity. In the clinical trial, treatment could be continued for a maximum of 2 years, but the optimum duration of therapy is not known. VI. Product Availability
    Intravenous reconstituted solution (Temodar): 100 mg • • Oral capsules (Temodar, generic): 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg VII.