SPRYCEL, Dasatinib Form

Dasatinib (Sprycel®, Phyrago™) is a kinase inhibitor.
FDA Approved Indication(s) Sprycel and Phyrago are indicated for the treatment of:
• Newly diagnosed adults with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase • Adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib • Adults with Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy Sprycel is indicated for the treatment of:
• Pediatric patients 1 year of age and older with Ph+ CML in chronic phase • Pediatric patients 1 year of age and older with newly diagnosed Ph+ ALL in combination with chemotherapy 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 dasatinib is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia (must meet all):

1. Diagnosis of one of the following (a or b):
   a. Ph+ (BCR-ABL1-positive) CML b. Ph+ (BCR-ABL1-positive) ALL;
2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age is one of the following (a or b): a. Sprycel: ≥ 1 year; b. Phyrago: ≥ 18 years;

3. Member does not have the following mutations: T315I/A, F317L/V/I/C or V299L;

   5. One of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D); Page 1 of 9

   CLINICAL POLICY Dasatinib

4. For brand Sprycel or Phyrago requests, member must use generic dasatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
5. Request meets one of the following (a, b, or c): a. Pediatrics, age < 18 years: Dose does not exceed the weight-based dosing in Section V; b. Adults, age ≥ 18 years: Dose does not exceed 180 mg per day; c. 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:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
   B. Gastrointestinal Stromal Tumor (off-label) (must meet all):
6. Diagnosis of unresectable, recurrent, progressive, or metastatic gastrointestinal stromal tumor (GIST; a soft tissue sarcoma);
7. Prescribed by or in consultation with an oncologist;
   3. Age is one of the following (a or b): a. Sprycel: ≥ 1 years; b. Phyrago: ≥ 18 years;
8. Failure of imatinib (Gleevec®) or Ayvakit®, unless clinically significant adverse effects are experienced or both are contraindicated;
   *Prior authorization is required for imatinib and Ayvakit.
9. For brand Sprycel or Phyrago requests, member must use generic dasatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
10. 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:
    Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
    C. Bone Cancer (off-label) (must meet all):
11. Diagnosis of metastatic chondrosarcoma or recurrent chordoma;
    2. Prescribed by or in consultation with an oncologist;
    3. Age is one of the following (a or b): a. Sprycel: ≥ 1 years; b. Phyrago: ≥ 18 years;

12. For chordoma, one of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib;
    b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D); Page 2 of 9

    CLINICAL POLICY Dasatinib

13. For brand Sprycel or Phyrago requests, member must use generic dasatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
14. 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:
    Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
    D. Off-Label Indications (must meet all):
15. Diagnosis of one of the following (a or b): a. Lymphoid, myeloid or mixed lineage neoplasms with eosinophilia (MLNE) and ABL1 rearrangement in blast or chronic phase; b. KIT-positive metastatic or unresectable melanoma as second-line or subsequent therapy (i.e., following BRAF-targeted therapy);
16. Prescribed by or in consultation with an oncologist or hematologist;
    
    3. Age is one of the following (a or b): a. Sprycel: ≥ 1 years; b. Phyrago: ≥ 18 years;
    4. One of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
17. For brand Sprycel or Phyrago requests, member must use generic dasatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
18. 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:
    Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
    E. 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: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or Page 3 of 9

    CLINICAL POLICY Dasatinib b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

20. 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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    II. Continued Approval
    A. All Indications in Section I (must meet all):
21. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Sprycel or Phyrago for a covered indication and has received this medication for at least 30 days;
    2. Member is responding positively to therapy;
    3. For brand Sprycel or Phyrago requests, member must use generic dasatinib, if available, unless contraindicated or clinically significant adverse effects are experienced
22. If request is for a dose increase, request meets one of the following (a, b, or c): a. Adults age ≥ 18 years, bone cancer, or GIST: New dose does not exceed 180 mg per day; b. Pediatrics age < 18 years for CML or ALL: New dose does not exceed weight- based dosing in Section V; c. 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:
    Medicaid/HIM - 12 months Commercial - 12 months or duration of request, whichever is less
    B. Other diagnoses/indications (must meet 1 or 2):
23. 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: CP.CPA.190 for commercial, 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: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

24. 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 Page 4 of 9

    CLINICAL POLICY Dasatinib of business: CP.CPA.09 for commercial, 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 – CP.CPA.09 for commercial, 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 ALL: acute lymphoblastic leukemia CML: chronic myelogenous leukemia FDA: Food and Drug Administration GIST: gastrointestinal stromal tumor MLNE: myeloid/lymphoid neoplasms with eosinophilia
    Ph+: positive Philadelphia chromosome 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. Dose Limit/ Maximum Dose Adults: 800 mg/day
    Pediatrics: 600 mg/day Drug Name Dosing Regimen imatinib (Gleevec)
    ALL: • Adult: 600 mg/day PO for relapsed / refractory Ph+ ALL • Pediatric: 340 mg/m2/day PO in combination with chemotherapy for newly diagnosed Ph+ ALL
    Chordoma: 400 mg PO BID CML: • Adult: o 400-600 mg/day PO for chronic phase o 600-800 mg/day PO for accelerated phase or blast crisis (800 mg given as 400 BID) • Pediatric: 340 mg/m2/day PO for chronic phase
    GIST: 400 mg PO QD to 400 mg PO BID
    MLNE: 100-400 mg PO QD [NCCN] GIST: 300 mg PO QD Ayvakit (avapritinib) 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. 300 mg/day Appendix C: Contraindications/Boxed Warnings None reported Page 5 of 9

    CLINICAL POLICY Dasatinib Appendix D: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH OK PA TN TX Yes Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
    the cancer or any symptom thereof of the covered person Applies to HIM requests only For stage 4 metastatic cancer and associated conditions Applies to HIM requests only For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration
    Indication Dosing Regimen CML Adults: • Chronic phase: 100-140 mg/day PO • Accelerated, myeloid phase, or lymphoid blast phase: 140-180 mg/day PO
    Pediatrics:
    Initial weight-based dosing PO QD: • Weight 10 to < 20 kg: 40 mg • Weight 20 to < 30 kg: 60 mg • Weight 30 to < 45 kg: 70 mg • Weight ≥ 45 kg: 100 mg Dose escalation PO QD: • Starting dose 40 mg can be escalated to 50 mg • Starting dose 60 mg can be escalated to 70 mg • Starting dose 70 mg can be escalated to 90 mg • Starting dose 100 mg can be escalated to 120 mg Adults: 140-180 mg/day PO Pediatrics:
    Weight-based dosing PO QD • Weight 10 to < 20 kg: 40 mg • Weight 20 to < 30 kg: 60 mg • Weight 30 to < 45 kg: 70 mg Page 6 of 9 ALL Maximum Dose Adults: 180 mg/day Pediatrics: 120 mg/day Adults: 180 mg/day Pediatrics: 100 mg/day

    CLINICAL POLICY Dasatinib Indication Dosing Regimen • Weight ≥ 45 kg: 100 mg Maximum Dose VI. Product Availability
    Tablets: 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg
    VII.