YONDELIS, Trabectedin Form

Trabectedin (Yondelis®) is an alkylating drug. FDA Approved Indication(s) Yondelis is indicated for the treatment of patients with unresectable or metastatic liposarcoma (LPS) or leiomyosarcoma (LMS) who received a prior anthracycline-containing regimen. Policy/Criteria Provider must submit documentation (including 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 Yondelis is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Soft Tissue Sarcoma (must meet all):

1. Diagnosis of one of the following soft tissue sarcomas (STS) (a or b) (see Appendix D for examples): a. STS that is unresectable or metastatic; b. Myxoid liposarcoma (LPS) that is one of the following (i, ii, or iii): i. Resectable; ii. High risk for metastatic disease; iii. Local recurrence;
2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. If uterine leiomyosarcoma (uLMS), prescribed in one of the following ways (a or b):
      a. As a single agent AND member has received a prior anthracycline-containing regimen (e.g., doxorubicin); b. In combination with doxorubicin;

3. Request meets one of the following (a or b): a. Dose does not exceed 1.5 mg/m2 body surface area every 3 weeks; 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
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   CLINICAL POLICY Trabectedin B. Other diagnoses/indications (must meet 1 or 2):

4. 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. Soft Tissue Sarcoma (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Yondelis for a covered indication and has received this medication for at least 30 days;
6. 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 1.5 mg/m2 body surface area every 3 weeks; 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):

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.
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   CLINICAL POLICY Trabectedin 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 policy – 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 FDA: Food and Drug Administration LMS: leiomyosarcoma LPS: liposarcoma STS: soft tissue sarcoma uLMS: uterine leiomyosarcoma Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen Varies Dose Limit/ Maximum Dose Varies uLMS - examples of anthracycline-containing regimens: doxorubicin ± gemcitabine, olaratumab, fosfamide, or dacarbazine; epirubicin; liposomal doxorubicin Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to trabectedin • Boxed warning(s): none reported Appendix D: Types and Examples of STSs Examples are drawn from the National Comprehensive Center Network (NCCN) Soft Tissue Sarcoma Guideline, which cites the 2020 World Health Organization classification of tumors, and the Yondelis compendium. • Smooth muscle tumors - LMS • Vascular tumors - angiosarcoma • Myo/fibroblastic tumors - solitary fibrous tumor • Skeletal muscle tumors - rhabdomyosarcoma • Adipocytic tumors – myxoid LPS
   o Begin in the adipose cells, usually occurring in the thigh and sometimes in the outer torso or buttocks o Myxoid LPS has a higher risk of metastasis to the spine compared to other STSs Page 3 of 6

   CLINICAL POLICY Trabectedin V. Dosage and Administration
   Indication Dosing Regimen LPS, LMS 1.5 mg/m2 (body surface area) as a 24-hour IV infusion every 21 days (3 weeks), until disease progression or unacceptable toxicity
   VI. Product Availability
   Single-dose vial with powder for injection: 1 mg Maximum Dose Varies VII.