Palbociclib (Ibrance) Form

Palbociclib (Ibrance®) is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6). FDA Approved Indication(s) Ibrance is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with: • An aromatase inhibitor as initial endocrine-based therapy; or • Fulvestrant in patients with disease progression following endocrine 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 Ibrance 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. Disease has all of the following characteristics (a, b, and c): a. HR-positive (i.e., estrogen receptor (ER) and/or progesterone receptor (PR) positive); b. HER2-negative; c. Advanced, recurrent, or metastatic;

   5. Ibrance is prescribed in combination with one of the following (a or b): a. Both of the following (i and ii): i. An aromatase inhibitor (e.g., letrozole, anastrozole, exemestane) as part of initial endocrine-based therapy; ii. If male, an agent that suppresses testicular steroidogenesis (e.g., gonadotropin-releasing hormone agonists); b. Fulvestrant;
   6. If member is a premenopausal or perimenopausal female, member has been treated with ovarian ablation or is receiving ovarian suppression (see Appendix D); Page 1 of 7

   CLINICAL POLICY Palbociclib

   7. Member has not previously experienced disease progression on a CDK 4/6 inhibitor therapy (e.g., Verzenio®, Kisqali®);
   8. Ibrance is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Verzenio, Kisqali);
   9. For brand Ibrance requests, member must use generic palbociclib, if available, unless contraindicated or clinically significant adverse effects are experienced;
   10. Request meets one of the following (a or b): a. Dose does not exceed both of the following on Days 1 to 21 of a 28-day cycle (i and ii): i. 125 mg per day; ii. 1 capsule or 1 tablet 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 – 6 months
       Commercial – 12 months or duration of request, whichever is less B. Soft Tissue Sarcoma (off-label) (must meet all):
   11. Diagnosis of retroperitoneal well-differentiated/dedifferentiated liposarcoma;
5. Prescribed by or in consultation with an oncologist;
6. Age ≥ 18 years;
7. Disease is unresectable;
8. Prescribed as a single agent;

9. Ibrance is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Verzenio, Kisqali);

   7. For brand Ibrance requests, member must use generic palbociclibb, if available, unless contraindicated or clinically significant adverse effects are experienced;
   8. 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 – 6 months Commercial – 12 months or duration of request, whichever is less 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 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 and CP.PMN.16 for Medicaid; or Page 2 of 7

   CLINICAL POLICY Palbociclib

   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 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 Ibrance for a covered indication and has received this medication for at least 30 days;
   4. Member is responding positively to therapy;
10. Ibrance is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Verzenio, Kisqali);
    4. If breast cancer, dose is ≥ 75 mg per day;
11. For brand Ibrance requests, member must use generic palbociclib, if available, unless contraindicated or clinically significant adverse effects are experienced;

12. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed both of the following on Days 1 to 21 of a 28-day cycle (i and ii): i. 125 mg per day; ii. 1 capsule or 1 tablet 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 – 12 months Commercial – 12 months or duration of request, whichever is less 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 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 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 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 policy – Page 3 of 7

    CLINICAL POLICY Palbociclib CP.CPA.09 for commercial and CP.PMN.53 for Medicaid or evidence of coverage documents; B. Use as adjuvant therapy in early-stage (stage 0-III) breast cancer. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CDK: cyclin-dependent kinase ER: estrogen receptor ET: endocrine therapy FDA: Food and Drug Administration HER2: human epidermal growth factor receptor 2 HR: hormone receptor Appendix B: Therapeutic Alternatives Not applicable
    iDFS: invasive disease-free survival LHRH: luteinizing hormone-releasing hormone NCCN: National Comprehensive Cancer Network PR: progesterone receptor Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • For disease progression while on a CDK4/6 inhibitor, there is no data to support retreatment with another CDK4/6 inhibitor-containing regimen. • Although the FDA labeled indication limits combination use with fulvestrant to second line for breast cancer, the NCCN recommends this combination as both first and second line (category 1). • • Beginning in April 2020, Pfizer announced they would be switching Ibrance from capsules to tablets. The tablets allow increased flexibility with administration, dose tracking (weekly blister packs), and address dietary concerns (do not contain lactose or gelatin). These formulations are bioequivalent. In the Phase 3 PALbociclib CoLlaborative Adjuvant Study (PALLAS) open-label trial, 5,760 patients with stage II-III HR+/HER2-negative early breast cancer were randomized to receive either 2 years of Ibrance with adjuvant endocrine therapy (ET), or ET alone. The primary objective was to compare invasive disease-free survival (iDFS) between arms. At the second interim data analysis, after a median follow-up of 23.7 months (351 events), iDFS was similar between the two arms, with 3-year iDFS of 88.2% for Ibrance plus ET, and 88.5% for ET alone (HR 0.93, 95% CI 0.76-1.15), crossing a pre-specified futility boundary. • Ovarian ablation may be accomplished by surgical oophorectomy or by ovarian irradiation. Ovarian suppression utilizes luteinizing hormone-releasing hormone (LHRH) agonists that result in suppression of luteinizing hormone and release of follicle- stimulating hormone from pituitary and reduction in ovarian estrogen production. LHRH agonists include goserelin and leuprolide. Page 4 of 7

    CLINICAL POLICY Palbociclib V. Dosage and Administration
    Indication Breast cancer Dosing Regimen 125 mg PO QD for 21 consecutive days followed by 7 days off treatment for a cycle of 28 days If a dose reduction to < 75 mg/day is required, therapy should be discontinued. Maximum Dose 125 mg/day VI. Product Availability
    • Capsules: 75 mg, 100 mg, 125 mg • Tablets: 75 mg, 100 mg, 125 mg VII.