Ribociclib (Kisqali), Ribociclib/Letrozole (Kisqali Femara) Form

Ribociclib (Kisqali®) is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6). Letrozole (Femara®) is an aromatase inhibitor. FDA Approved Indication(s) Kisqali (in combination with an aromatase inhibitor) and Kisqali Femara are indicated as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. Kisqali is also indicated in combination with fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy for the treatment of postmenopausal women or men with HR-positive, HER2-negative advanced or 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 Kisqali and Kisqali Femara are 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. If request is for Kisqali, therapy is prescribed in combination with one of the following (a or b): a. An aromatase inhibitor (e.g., letrozole, anastrozole, exemestane) as part of initial endocrine-based therapy; b. Fulvestrant;
   6. If request is for Kisqali Femara, prescribed as initial endocrine-based therapy; Page 1 of 7

   CLINICAL POLICY Ribociclib, Ribociclib/Letrozole

   7. If male and receiving an aromatase inhibitor, therapy is prescribed in combination with an agent that suppresses testicular steroidogenesis (e.g., gonadotropin-releasing hormone agonists);
   8. If member is a premenopausal female, member has been treated with ovarian ablation or is receiving ovarian suppression (see Appendix D);
   9. Member has not previously experienced disease progression on a CDK 4/6 inhibitor therapy (e.g., Verzenio®, Ibrance®);
   10. The requested agent is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Verzenio, Ibrance);
   11. For brand Kisqali requests, member must use generic ribociclib, if available, unless contraindicated or clinically significant adverse effects are experienced;
   12. Request meets one of the following (a, b, or c): a. For Kisqali: Dose does not exceed Kisqali 600 mg (3 tablets) per day for 21 days of each 28-day cycle; b. For Kisqali Femara: Dose does not exceed Kisqali 600 mg (3 tablets) per day for 21 days of each 28-day cycle and Femara 2.5 mg (1 tablet) per day for each 28- day cycle; 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. Other diagnoses/indications (must meet 1 or 2):
   13. 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
   14. 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):
       Page 2 of 7

   CLINICAL POLICY Ribociclib, Ribociclib/Letrozole

   1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Kisqali or Kisqali Femara for breast cancer and has received this medication for at least 21 days;
5. Member is responding positively to therapy;
6. Dose of Kisqali is ≥ 200 mg per day;

7. The requested agent is not prescribed concurrently with another CDK 4/6 inhibitor therapy (e.g., Verzenio, Ibrance);

   5. For brand Kisqali requests, member must use generic ribociclib, if available, unless contraindicated or clinically significant adverse effects are experienced;
   6. If request is for a dose increase, request meets one of the following (a, b, or c): a. For Kisqali: Dose does not exceed Kisqali 600 mg (3 tablets) per day for 21 days of each 28-day cycle; b. For Kisqali Femara: New dose does not exceed Kisqali 600 mg (3 tablets) per day for 21 days of each 28-day cycle and Femara 2.5 mg (1 tablet) per day for each 28-day cycle; c. New dose is supported by practice guideline 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):
   7. 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
   8. 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. Page 3 of 7

   CLINICAL POLICY Ribociclib, Ribociclib/Letrozole IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CDK: cyclin-dependent kinase ER: estrogen 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 PR: progesterone receptor Appendix C: Contraindications/Boxed Warnings • Contraindication(s): Kisqali Femara only – known hypersensitivity to letrozole, or to any excipients of Femara • Boxed warning(s): 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. • The NCCN no longer supports the use of Kisqali with tamoxifen (previously category 1; removed from the breast cancer guidelines as of v1.2020). In addition, there is a warning in Kisqali’s prescribing information noting concerns for increased QT prolongation observed with concomitant use in the MONALEESA-7 trial. • 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. V. Dosage and Administration
   Drug Name Dosing Regimen Ribociclib (Kisqali) 600 mg PO QD for 21 consecutive days Maximum Dose 600 mg/day Ribociclib/letrozole (Kisqali Femara) followed by 7 days off 600 mg Kisqali PO QD for 21 consecutive days followed by 7 days off Kisqali: 600 mg/day If a dose reduction to < 200 mg/day is required, therapy should be discontinued. 2.5 mg Femara PO QD for a 28-day cycle Femara: 2.5 mg/day VI. Product Availability
   Drug Name Ribociclib (Kisqali) Ribociclib/letrozole (Kisqali Femara) Tablets: 200 mg ribociclib, 2.5 mg letrozole Availability
   Tablet: 200 mg Page 4 of 7

   CLINICAL POLICY Ribociclib, Ribociclib/Letrozole VII.