PIQRAY, Alpelisib Form

Alpelisib (Piqray®, Vijoice®) is a phosphoinositide 3-kinase (PI3K) inhibitor. FDA Approved Indication(s) Piqray is indicated in combination with fulvestrant for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA- mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.
Vijoice is indicated for the treatment of adult and pediatric patients 2 years of age or older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy.This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 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 Piqray and Vijoice are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Breast Cancer (must meet all):

1. Request is for Piqray;
   2. Diagnosis of breast cancer;
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. Disease has all of the following characteristics (a, b, c, and d): a. HR-positive (i.e., estrogen or progesterone receptor [ER/PR]-positive); b. HER2-negative; c. Advanced (locally recurrent) or metastatic;
      d. Positive for PIK3CA mutation;

2. Piqray is prescribed in combination with fulvestrant;

   7. Disease has progressed on or after an endocrine-based therapy regimen (see Appendix B); Page 1 of 9

   CLINICAL POLICY Alpelisib

3. For Piqray requests, member must use alpelisib, if available, unless contraindicated or clinically significant adverse effects are experienced;
4. Request meets one of the following (a or b): a. Dose does not exceed 300 mg (two 150 mg tablets) 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. PIK3CA Related Overgrowth Spectrum (must meet all):
5. Request is for Vijoice;
   2. Diagnosis of PROS;
   3. Age ≥ 2 years;
   4. Member meets one of the following (a or b):
      a. Documented evidence for PIK3CA gene mutation; b. If unable to perform biopsy to confirm PIK3CA gene mutation, member meets all of the following (i, ii, and iii): i. Congenital or early childhood onset (birth to the age of eight); ii. Overgrowth that is sporadic and mosaic (other terms: patchy, irregular); iii. Either of any two clinical spectrum features from Category A or any one isolated feature from Category B (see Appendix E);
6. Member’s condition is severe or life-threatening requiring systemic therapy as determined by treating physician;
7. For non-cutaneous lesions, member has at least one target lesion identified on imaging within the last 6 months;
8. Dose does not exceed any of the following (a, b, or c):
   a. Age 2-5 years: 50 mg (1 tablet) per day; b. Age 6-17 years: 125 mg (1 tablet) per day; c. Age ≥ 18 years: 250 mg (two 125 mg tablets) per day. Approval duration: 6 months C. Other diagnoses/indications (must meet 1 or 2):

9. 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 2 of 9

   CLINICAL POLICY Alpelisib

10. 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. Breast Cancer (must meet all):
11. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Piqray for breast cancer and has received this medication for at least 30 days;
12. Request is for Piqray;
    3. Member is responding positively to therapy;
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 300 mg (two 150 mg tablets) 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 B. PIK3CA Related Overgrowth Spectrum (must meet all):
13. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
14. Request is for Vijoice;
    3. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following:
       a. Reduction in size, volume, and/or total number of measurable lesions from baseline via subsequent imaging scan; b. Improvement in at least one sign, symptom, or complication of PROS (e.g., pain, fatigue, vascular malformation, limb asymmetry, disseminated intravascular coagulation); c. Improvement in functional status (e.g., mobility, performance, work/school attendance);

15. If request is for a dose increase, new dose does not exceed any of the following (a, b, or c):
    a. Age 2-5 years: 50 mg (1 tablet) per day; b. Age 6-17 years: 125 mg (1 tablet) per day; c. Age ≥ 18 years: 250 mg (two 125 mg tablets) per day. Approval duration: 12 months
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    CLINICAL POLICY Alpelisib C. Other diagnoses/indications (must meet 1 or 2):

16. 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

17. 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 ER: estrogen receptor FDA: Food and Drug Administration HER2: human epidermal growth factor receptor 2 HR: hormone receptor NCCN: National Comprehensive Cancer Network PR: progesterone receptor PROS: PIK3CA-related overgrowth spectrum 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 Endocrine Therapy anastrozole (Arimidex®) exemestane (Aromasin®) Fareston® (toremifene) fulvestrant (Faslodex®) 1 mg PO QD 25 mg PO QD 60 mg PO QD 500 mg IM into the buttocks slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, 29 and once monthly thereafter 1 mg/day 25 mg/day 60 mg/day 500 mg/day Page 4 of 9

    CLINICAL POLICY Alpelisib Drug Name Dosing Regimen Dose Limit/ Maximum Dose 2.5 mg PO QD 20 to 40 mg PO QD Endocrine Therapy letrozole (Femara®) tamoxifen (Nolvadex®, Soltamox®) megestrol acetate NCCN-recommended CDK4/6 inhibitors to be used in combination with aromatase inhibitors as first-line therapy Kisqali® (ribociclib) Verzenio® (abemaciclib) Ibrance® (palbociclib) 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. NCCN category 1 recommendation 2.5 mg/day 40 mg/day 40 mg PO QID 160 mg/day Varies Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): severe hypersensitivity to Piqray or Vijoice or to any of its components • Boxed warning(s): none reported Appendix D: General Information
    Subdivisions of PROS
    • CLAPO syndrome: capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry, and partial/generalized overgrowth • CLOVES syndrome: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal • Diffuse capillary malformation with overgrowth
    • Dysplastic megalencephaly
    • Fibroadipose hyperplasia/fibroadipose overgrowth/hemihyperplasia-multiple lipomatosis syndrome • Fibroadipose vascular anomaly
    • Facial infiltrating lipomatosis • Hemimegalencephaly
    • Klippel-Trenaunay syndrome • Lipomatosis of nerve
    • Macodactyly • Megalencephaly-capillary malformation syndrome • Muscular hemihyperplasia Page 5 of 9

    CLINICAL POLICY Alpelisib Appendix E: National Institutes of Health (NIH) Workshop Recommended Clinical Features of PROS
    Category A (spectrum) - 2 or more features • Overgrowth: adipose, muscle, nerve, Category B (isolated features) – any 1 feature • Large, isolated lymphatic malformation
    • Isolated macrodactyly or overgrown, splayed feed/hands, overgrown limbs
    skeletal
    • Vascular malformations: capillary, venous, arteriovenous malformation, lymphatic
    • Epidermal nevus
    V. Dosage and Administration
    • Truncal adipose overgrowth
    • Hemimegaloencephaly (bilateral), dysplastic megalencephaly, focal cortical dysplasia
    • Epidermal nevus
    • Seborrheic keratoses
    • Benign lichenoid keratoses
    Drug Name Indication Dosing Regimen Piqray Breast cancer PROS Vijoice In combination with fulvestrant: 300 mg PO daily with food Pediatric patients (2 to < 18 years of age): 50 mg PO daily with food. Consider a dose increase to 125 mg PO daily in pediatric patients > 6 years old for response optimization after 24 weeks of treatment with Vijoice at 50 mg once daily Maximum Dose 300 mg/day • Age 2 – 5: 50 mg/day • Age 6-17: 125 mg/day • Age ≥ 18: 250 mg/day Adult patients: 250 mg PO daily with food VI. Product Availability
    Drug Name Availability
    Piqray Vijoice Tablets: 50 mg, 150 mg, 200 mg Tablets: 50 mg, 125 mg, 200 mg VII.