XALKORI, Crizotinib Form

Crizotinib (Xalkori®) is a kinase inhibitor. FDA Approved Indication(s) Xalkori is indicated for the treatment of:
• Adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. • Pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. • Adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. Limitation(s) of use: The safety and efficacy of Xalkori have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. 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 Xalkori is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Non-Small Cell Lung Cancer (must meet all):

1. Diagnosis of recurrent, advanced or metastatic NSCLC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is ALK, ROS1, MET exon 14 skipping, or high-level MET amplification positive;
2. Prescribed as a single agent;
   6. For Xalkori requests, member must use generic crizotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

3. Request meets one of the following (a or b):* a. Dose does not exceed both of the following (i and ii): i. 500 mg per day; ii. One of the following (1 or 2): 1) 2 capsules per day; Page 1 of 8

   CLINICAL POLICY Crizotinib 2) 6 pellets 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 – 6 months
   Commercial – 12 months or duration of request, whichever is less B. Anaplastic Large Cell Lymphoma (must meet all):

4. Diagnosis of relapsed or refractory ALCL (a peripheral T-cell lymphoma);
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 1 year;
   4. Disease is ALK-positive;
   5. Prescribed as a single agent;
   6. For Xalkori requests, member must use generic crizotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
5. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
   i. 560 mg/m2 per day, up to a maximum of 1,000 mg per day; ii. One of the following (1 or 2): 1) 4 capsules per day; 2) 8 pellets 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 – 6 months Commercial – 12 months or duration of request, whichever is less
   C. Inflammatory Myofibroblastic Tumor (must meet all):
6. Diagnosis of IMT;
   
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 1 year;
   4. Disease is ALK-positive;
   5. Prescribed as a single agent;
   6. For Xalkori requests, member must use generic crizotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

7. Request meets one of the following (a, b, or c):*
   a. For pediatric members, dose does not exceed both of the following (i and ii):
   i. 560 mg/m2 per day, up to a maximum of 1,000 mg per day;
   ii. One of the following (1 or 2): 1) 4 capsules per day; 2) 8 pellets per day; b. For adult members, dose does not exceed both of the following (i and ii):
   i. 500 mg per day;
   ii. One of the following (1 or 2): 1) 2 capsules per day; Page 2 of 8

   CLINICAL POLICY Crizotinib 2) 6 pellets 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
   D. Off-Label NCCN Compendium Recommended Indications (must meet all):

8. Prescribed for one of the following diagnoses (a - c): a. Histiocytic neoplasm (Erdheim-Chester Disease, Langerhans Cell Histiocytosis, Rosai-Dorfman Disease);
   b. Cutaneous melanoma; c. Uterine sarcoma and both (i and ii): i. Presence of IMT; ii. Disease is advanced, recurrent, metastatic, or inoperable;
9. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. For histiocytic neoplasm or uterine sarcoma, disease is ALK-positive;
   5. For cutaneous melanoma, all of the following (a, b, and c): a. Disease is metastatic or unresectable; b. Disease is ROS1-positive; c. Xalkori is prescribed as second-line or subsequent therapy;
10. Prescribed as a single agent;
    7. For Xalkori requests, member must use generic crizotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
11. 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):

12. 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 Page 3 of 8

    CLINICAL POLICY Crizotinib

13. 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):
14. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Xalkori for a covered indication and has received this medication for at least 30 days;
15. Member is responding positively to therapy;
    3. For Xalkori requests, member must use generic crizotinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
16. If request is for a dose increase, request meets one of the following (a, b, or c): a. NSCLC and adult IMT: New dose does not exceed both of the following (i and ii): i. 500 mg per day; ii. One of the following (1 or 2): 1) 2 capsules per day; 2) 6 pellets per day; b. ALCL and pediatric IMT: New dose does not exceed both of the following (i and ii):
    i. 560 mg/m2 per day, up to a maximum of 1,000 mg per day; ii. One of the following (1 or 2): 1) 4 capsules per day; 2) 8 pellets per day; 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):

17. 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 Page 4 of 8

    CLINICAL POLICY Crizotinib

18. 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 ALK: anaplastic lymphoma kinase ALCL: anaplastic large cell lymphoma
    FDA: Food and Drug Administration IMT: inflammatory myofibroblastic tumor MET: mesenchymal-epithelial transition NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer ROS1: ROS proto-oncogene 1 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 Dose Limit/ Maximum Dose Varies Cutaneous Melanoma Opdivo® (nivolumab) ± Yervoy® (ipilimumab) Opdivo® (nivolumab) + Opdualag® (relatlimab- rmbw) Keytruda® (pembrolizumab) 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. Varies
    Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • MET amplification is an oncogenic driver occurring in 1% to 5% of NSCLCs that confers a poor prognosis. High-level MET amplification is an emerging biomarker to identify novel therapies for patients with metastatic NSCL per NCCN. The definition of high- level MET amplification is evolving and may differ according to the assay used for Page 5 of 8

    CLINICAL POLICY Crizotinib testing. For NGS-based results, a copy number greater than 10 is consistent with high- level MET amplification. (NCCN NSCLC Guideline Version 1.2023) V. Dosage and Administration
    Indication NSCLC ALCL IMT Dosing Regimen 250 mg PO BID 280 mg/m2 PO BID Pediatric: 280 mg/m2 PO BID Adult: 250 mg PO BID Maximum Dose 500 mg/day 1,000 mg/day Pediatric: 1,000 mg/day Adult: 500 mg/day VI. Product Availability
    Capsules: 200 mg, 250 mg Oral pellets: 20 mg, 50 mg, 150 mg VII.