TYKERB, Lapatinib Ditosylate Form

Lapatinib (Tykerb®) is a kinase inhibitor. FDA Approved Indication(s) Tykerb is indicated in combination with: • Capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress human epidermal growth factor receptor 2 (HER2) and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. • Letrozole for the treatment of postmenopausal women with hormone receptor (HR)-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated. Limitation(s) of use:
• Patients should have disease progression on trastuzumab prior to initiation of treatment with Tykerb in combination with capecitabine. • Tykerb in combination with an aromatase inhibitor has not been compared to a trastuzumab- containing chemotherapy regimen for the treatment of metastatic breast cancer. 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 Tykerb is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Diagnosis of breast cancer;
2. Prescribed by or in consultation with an oncologist;
3. Age ≥ 18 years;

4. Member meets both of the following (a and b): a. Disease is recurrent, advanced, or metastatic (stage IV); b. HER2-positive;

   5. Tykerb is prescribed in combination with one of the following (a, b, or c):* a. Capecitabine, and one of the following (i or ii): i. Member has received prior therapy; ii. Member has extensive brain metastases; Page 1 of 7

   CLINICAL POLICY Lapatinib b. Trastuzumab, and member has received at least 3 prior therapies; c. Both of the following (i and ii): i. If HR-positive, an aromatase inhibitor (e.g., anastrozole, letrozole, exemestane); ii. If male, an agent that suppresses testicular steroidogenesis (e.g., gonadotropin-releasing hormone agonists); *Prior authorization may be required

   6. If member is a premenopausal female, member has been treated with ovarian ablation or is receiving ovarian suppression (see Appendix D);
   7. For brand Tykerb requests, member must use generic lapatinib, unless contraindicated or clinically significant adverse effects are experienced;
   8. Request meets one of the following (a or b):
      a. Dose does not exceed 1,500 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 – 6 months Commercial – 12 months or duration of request, whichever is less B. Bone Cancer (off-label) (must meet all):
5. Diagnosis of recurrent chordoma;
6. Prescribed by or in consultation with an oncologist;
7. Age ≥ 18 years;
8. Disease is EGFR-positive;
9. Prescribed as a single agent;
10. For brand Tykerb requests, member must use generic lapatinib, unless contraindicated or clinically significant adverse effects are experienced;
    
    7. 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. Colorectal Cancer (off-label) (must meet all):
    8. Diagnosis of unresectable, advanced, or metastatic colorectal cancer and both of the following (a and b): a. Disease is HER2 positive; b. Disease is RAS (i.e., both KRAS and NRAS) and BRAF wild-type;
    9. Prescribed by or in consultation with an oncologist;
11. Age ≥ 18 years;

12. No previous use of a HER2 inhibitor therapy (e.g., trastuzumab, Kadcyla®, Tykerb, Perjeta®);

    5. Prescribed in combination with trastuzumab;Prior authorization may be required. Page 2 of 7

    CLINICAL POLICY Lapatinib

    6. For brand Tykerb requests, member must use generic lapatinib, unless contraindicated or clinically significant adverse effects are experienced;
    7. 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. Other diagnoses/indications (must meet 1 or 2):
    8. 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
    9. 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):
    10. Currently receiving medication via Centene benefit or documentation supports that member is currently receiving Tykerb for a covered indication and has received this medication for at least 30 days;
    11. Member is responding positively to therapy;

13. For brand Tykerb requests, member must use generic lapatinib, unless contraindicated or clinically significant adverse effects are experienced;

    4. If request is for a dose increase, meets one of the following (a or b):
       a. New dose does not exceed 1,500 mg per day;
       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:
       Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less Page 3 of 7

    CLINICAL POLICY Lapatinib B. 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.
       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 EGFR: epidermal growth factor receptor FDA: Food and Drug Administration HER2: human epidermal growth factor receptor 2
       Appendix B: Therapeutic Alternatives
       Not applicable HR: hormone receptor NCCN: National Comprehensive Cancer Network Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known severe hypersensitivity (e.g., anaphylaxis) to this product or any of its components • Boxed warning(s): hepatotoxicity Appendix D: General Information • NCCN recommendations in breast cancer: o The NCCN recommends that men with HR-positive breast cancer be treated similarly to postmenopausal women, except that the use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis. o The NCCN supports use of Tykerb in premenopausal women with HR-positive breast cancer when used concomitantly with an aromatase inhibitor. Along with this Page 4 of 7

    CLINICAL POLICY Lapatinib combination therapy, patients should also be treated with ovarian ablation/suppression. Ovarian ablation can be achieved with surgical oophorectomy or ovarian irradiation. Ovarian suppression can be achieved with luteinizing hormone-releasing hormone agonists (e.g., goserelin, leuprolide). o The NCCN also recommends use of Tykerb in combination with capecitabine for the treatment of recurrent brain metastases in patients with breast cancer that is responsive to Tykerb. • HR-positive can be either estrogen receptor (ER)- or progesterone receptor (PR)-positive. V. Dosage and Administration
    Indication Dosing Regimen Breast cancer
    Advanced or metastatic: 1,250 mg PO QD on Days 1-21 continuously in combination with capecitabine 2,000 mg/m2/day (administered PO in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21-day cycle HER2-positive: 1,500 mg PO QD continuously in combination with letrozole 2.5 mg PO QD Maximum Dose 1,500 mg/day 5,500 mg/day if taking a strong CYP3A4 inducer
    500 mg/day if taking a strong CYP3A4 inhibitor VI. Product Availability
    Tablet: 250 mg VII.