BOSULIF, Bosutinib Form

Bosutinib (Bosulif®) is a kinase inhibitor.
FDA Approved Indication(s) Bosulif is indicated for the treatment of patients with: • Adult and pediatric patients one year of age or older with chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML), newly diagnosed or resistant, or intolerant to prior therapy. • Adult patients with accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy. 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 Bosulif is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Myelogenous Leukemia (must meet all):

1. Diagnosis of Ph+ (BCR-ABL1-positive) CML;
2. Prescribed by or in consultation with an oncologist or hematologist;
3. One of the following (a or b);
   a. Age ≥ 1 years with chronic phase CML; b. Age ≥ 18 years with accelerated phase (AP), or blast phase (BP) CML;
   4. Member does not have the following mutations: T315I, V299L, G250E, or F317L;

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);

   6. For brand Bosulif requests, member must use generic bosutinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
   7. Request meets one of the following (a, b, or c):* a. For an adult member, dose does not exceed 600 mg per day; b. For a pediatric member, dose not exceed the body surface area (BSA)-based dosing listed in section V; Page 1 of 8

   CLINICAL POLICY Bosutinib 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. Acute Lymphoblastic Leukemia (off-label) (must meet all):

   1. Diagnosis of Ph+ (BCR-ABL1-positive) acute lymphoblastic leukemia (ALL);
5. Prescribed by or in consultation with an oncologist or hematologist;
6. Member does not have the following mutations: T315I, V299L, G250E, or F317L;
7. 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);
   5. For brand Bosulif requests, member must use generic bosutinib, if available, 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:
      Medicaid/HIM - 6 months Commercial - 12 months or duration of request, whichever is less C. Myeloid/Lymphoid Neoplasms (off-label) (must meet all):
   7. Diagnosis of myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase fusion genes;
   8. Prescribed by or in consultation with an oncologist or hematologist;
8. Disease is BCR-ABL1-positive;

9. 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);

   5. For brand Bosulif requests, member must use generic bosutinib, if available, 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:
      Medicaid/HIM - 6 months Commercial - 12 months or duration of request, whichever is less Page 2 of 8

   CLINICAL POLICY Bosutinib D. Other diagnoses/indications (must meet 1 or 2):

   1. 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
   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: CP.CPA.09 for commercial, 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):
   3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Bosulif for a covered indication and has received this medication for at least 30 days;
   4. Member is responding positively to therapy;

10. For brand Bosulif requests, member must use generic bosutinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

    4. If request is for a dose increase, new dose does not exceed the following (a or b): a. Dose does not exceed 600 mg per day; 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:
       Medicaid/HIM - 12 months Commercial - 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):
    5. 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 8

    CLINICAL POLICY Bosutinib 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

    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: 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
       AP: accelerated phase BP: blast phase CML: chronic myelogenous leukemia CP: chronic phase FDA: Food and Drug Administration MLNE: Myeloid/lymphoid neoplasms with eosinophilia
       Ph+: Philadelphia chromosome-positive 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 800 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
       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
       MLNE: 100-400 mg PO QD [NCCN] Page 4 of 8

    CLINICAL POLICY Bosutinib 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): Hypersensitivity to Bosulif Boxed warning(s): None reported Appendix D: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH PA TN TX 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 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
    Adult: 400 mg/day PO
    Indication: Dosing Regimen Newly diagnosed Ph+ CP CML
    Pediatrics: body surface area (BSA) dosing
    • < 0.55 m2 = 150 mg/day PO 2 • 0.55 to <0.75 m = 200 mg/day PO • 0.75 to 0.9 m2 = 250 mg/day PO • 0.9 to <1.1 m2 = 300 mg/day PO • ≥1.1 m2 = 400 mg/day PO Adults: 500 mg PO QD Maximum Dose Adults:600 mg/day Pediatrics: BSA dosing • < 0.55 m2 = 250 mg/day • 0.55 to <0.75 m2 = 200 mg/day 2 • 0.75 to 0.9 m = 350 mg/day • 0.9 to <1.1 m2 = 400 mg/day • ≥1.1 m = 600 mg/day 2 Adults: 600 mg/day Ph+ CP CML With resistance or intolerance to previous therapy Pediatrics: BSA dosing
    • <0.55 m2 = 200 mg/day PO
    • 0.55 to <0.63 m2 = 250 mg/day PO • 0.63 to < 0.75 m2 =300 mg/day PO • 0.75 to <0.9 m2 = 350 mg/day PO • 0.9 to <1.1 m2 = 400 mg/day PO Pediatrics: BSA dosing
    • <0.55 m2 = 300 mg/day • 0.55 to <0.63 m2 = 350 mg/day • 0.63 to < 0.75 m2 =400 mg/day
    • 0.75 to <0.9 m2 = 450 mg/day • 0.9 to <1.1 m2 = 500 mg/day
    Page 5 of 8

    Maximum Dose • ≥1.1 m2 = 600 mg/day
    Adults: 600mg/day
    CLINICAL POLICY Bosutinib Indication: Dosing Regimen • ≥1.1 m2 = 500 mg/day PO Adults: 500mg/day PO
    AP, or BP Ph+ CML with resistance or intolerance to prior therapy VI. Product Availability
    Tablets: 100 mg, 400 mg, 500 mg Capsules: 50 mg, 100 mg
    VII.