TORISEL, Temsirolimus Form

Temsirolimus for injection (Torisel®) is a kinase inhibitor. FDA Approved Indication(s) Torisel is indicated for the treatment of advanced renal cell carcinoma (RCC). 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 Torisel is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Renal Cell Carcinoma (must meet all):

1. Diagnosis of advanced RCC (i.e., relapsed, metastatic or stage IV disease);
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Prescribed as a single agent;
   5. Member has at least 3 prognostic risk factors (Appendix D);
   6. For brand Torisel requests, member must use generic temsirolimus injection, unless contraindicated or clinically significant adverse effects are experienced;
2. Request meets one of the following (a or b): a. Dose does not exceed 25 mg per week (50 mg per week if member is on concomitant strong CYP3A4 inducer such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital); 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. Endometrial Carcinoma (off-label) (must meet all):
3. Diagnosis of one of the following (a or b): a. Endometrial carcinoma; b. Uterine Sarcoma;

4. Prescribed by or in consultation with an oncologist;

   3. Age ≥ 18 years; Page 1 of 6

   CLINICAL POLICY Temsirolimus

5. Prescribed as a single agent;
   5. For brand Torisel requests, member must use generic temsirolimus injection, unless contraindicated or clinically significant adverse effects are experienced;
6. Request meets one of the following (a or b): a. Dose does not exceed 25 mg per week (50 mg per week if member is on concomitant strong CYP3A4 inducer such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital). 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. Soft Tissue Sarcoma (off-label) (must meet all):
7. Diagnosis of one of the following soft tissue sarcomas (a, b, c, or d): a. Locally advanced, unresectable, or metastatic malignant perivascular epithelioid cell tumor (PEComa);
   b. Recurrent angiomyolipoma; c. Lymphangioleiomyomatosis; d. Non-pleomorphic rhabdomyosarcoma;
8. Prescribed by or in consultation with an oncologist;
   
   3. Age ≥ 18 years;
   4. Prescribed in one of the following ways (a or b): a. For non-pleomorphic rhabdomyosarcoma: In combination with cyclophosphamide and vinorelbine; b. For all other indications: As a single agent;
9. For brand Torisel requests, member must use generic temsirolimus injection, unless contraindicated or clinically significant adverse effects are experienced;
10. Request meets one of the following (a or b): a. Dose does not exceed 25 mg per week (50 mg per week if member is on concomitant strong CYP3A4 inducer such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital); 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 D. 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 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 Page 2 of 6

    CLINICAL POLICY Temsirolimus

12. 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):
13. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Torisel for a covered indication and has received this medication for at least 30 days;
14. Member is responding positively to therapy;
    3. For brand Torisel requests, member must use generic temsirolimus injection, unless contraindicated or clinically significant adverse effects are experienced;
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 25 mg per week (50 mg per week if member is on concomitant strong CYP3A4 inducer such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital);
       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):

15. 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.PHAR.21 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
       Page 3 of 6

    CLINICAL POLICY Temsirolimus IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network
    Appendix B: Therapeutic Alternatives
    Not applicable PEComa: perivascular epithelioid cell tumor RCC: renal cell carcinoma Appendix C: Contraindications/Black Box Warnings • Contraindication(s): bilirubin > 1.5 times the upper limit of normal • Boxed warning(s): none reported Appendix D: General Information • At least 3 of the following 6 prognostic risk factors (based on the inclusion criteria in Torisel pivotal trial): o Interval of less than 1 year from time of RCC diagnosis to start of systemic therapy o Karnofsky performance status score of 60 or 70 o Hemoglobin level below normal (e.g., men < 13.5 g/dL, women < 12 g/dL)
    o Corrected serum calcium level > 10 mg/dL (2.5 mmol per liter) o Serum lactate dehydrogenase level > 1.5 times the upper limit of normal o More than one metastatic organ site V. Dosage and Administration
    Indication Dosing Regimen RCC 25 mg administered as an IV infusion over a 30-60 minute period once a week.
    Consider 50 mg once a week if concomitant strong CYP3A4 inducer (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital).
    VI. Product Availability
    Kit: single-use vial 25 mg/mL temsirolimus; diluent vial 1.8 mL
    Maximum Dose 50 mg/week VII.