VARUBI, Rolapitant HCl Form

Rolapitant (Varubi ™) is a substance P/neurokinin 1 (NK1) receptor antagonist. FDA Approved Indication(s) Varubi is indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.
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 Varubi is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Prevention of Nausea and Vomiting Associated with Cancer Chemotherapy (must meet all):

1. Prescribed for the prevention of chemotherapy-induced nausea/vomiting;
2. Age ≥ 18 years;

3. Member is scheduled to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D);

   4. Member meets one of the following (a or b): a. Failure of aprepitant, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for aprepitant b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix E);
   5. Prescribed in combination with a serotonin (5-HT3) receptor antagonist (ondansetron is preferred) and dexamethasone;
   6. Dose does not exceed 180 mg (2 tablets) every 2 weeks. Approval duration: Projected duration of chemotherapy 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): Page 1 of 7

   CLINICAL POLICY Rolapitant a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

4. 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Prevention of Nausea and Vomiting Associated with Cancer Chemotherapy (must meet all):
5. 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);
6. Member is responding positively to therapy;
7. Member continues to receive moderately to highly emetogenic cancer chemotherapy (see Appendix D);
   4. Prescribed in combination with a 5-HT3 receptor antagonist (ondansetron is preferred) and dexamethasone;
   5. If request is for a dose increase, new dose does not exceed 180 mg (2 tablets) every 2 weeks. Approval duration: Projected duration of chemotherapy B. Other diagnoses/indications (must meet 1 or 2):
   6. 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: 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: 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
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   CLINICAL POLICY Rolapitant 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 – 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 5-HT3: serotonin 5-hydroxytryptamine, type 3 FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network
   NK1: neurokinin 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 and may require prior authorization.
   Drug Name Dosing Regimen Dose Limit/ Maximum Dose Per chemotherapy cycle: Day 1: 125 mg Days 2 and 3: 80 mg aprepitant (Emend®) 125 mg PO on day 1 and then 80 mg PO on days 2 and 3 of each chemotherapy cycle 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o CYP2D6 substrates with a narrow therapeutic index (e.g., thioridazine and pimozide) o Pediatric patients less than 2 years of age due to irreversible impairment of sexual development and fertility in juvenile rats • Boxed warning(s): none reported Appendix D: American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) Recommendations in Oncology • Minimal emetic risk chemotherapy: No routine prophylaxis is recommended. • Low emetic risk chemotherapy: Recommended options include dexamethasone (recommended by both ASCO and NCCN) or metoclopramide, prochlorperazine, or a 5- HT3 receptor antagonist (recommended by NCCN only). NK1 receptor antagonists are not included in low risk antiemetic recommendations. • Moderate emetic risk chemotherapy: 5-HT3 receptor antagonists and dexamethasone may be used in combination and with or without NK1 receptor antagonists. Olanzapine may also be used in combination with palonosetron and dexamethasone. o Examples of moderate emetic risk chemotherapy: azacitidine, bendamustine, carboplatin, clofarabine, cyclophosphamide ≤ 1,500 mg/m2, cytarabine > 200 mg/m2, daunorubicin, doxorubicin < 60 mg/m2, epirubicin ≤ 90 mg/m2, idarubicin, ifosfamide, irinotecan, oxaliplatin Page 3 of 7

   CLINICAL POLICY Rolapitant • High emetic risk chemotherapy: NK1 receptor antagonists are recommended for use in combination with 5-HT3 receptor antagonists and dexamethasone. Olanzapine may also be used in combination with 5-HT3 receptor antagonists, dexamethasone, and/or NK1 receptor antagonists. o Examples of high emetic risk chemotherapy: carmustine, cisplatin, cyclophosphamide

   1,500 mg/m2, dacarbazine, mechlorethamine, streptozocin • Breakthrough emesis: Per NCCN, an agent from a different drug class is recommended to be added to the current antiemetic regimen. Drug classes include atypical antipsychotics (olanzapine), benzodiazepines (lorazepam), cannabinoids (dronabinol, nabilone), phenothiazines (prochlorperazine, promethazine), 5-HT3 receptor antagonists (dolasetron, ondansetron, granisetron), steroids (dexamethasone), or haloperidol, metoclopramide, scopolamine. An NK1 receptor antagonist may be added to the prophylaxis regimen of the next chemotherapy cycle if not previously included. Appendix E: States with Regulations against Redirections in Stage IV or Metastatic Cancer State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
   the cancer or any symptom thereof of the covered person Applies to Commercial and HIM requests only For stage 4 metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration Indication Prevention of chemotherapy- induced nausea and vomiting Dosing Regimen 180 mg as a single dose 2 hours prior to the initiation of each chemotherapy, but at no less than 2 week intervals. Maximum Dose 180 mg Administer in combination with dexamethasone and a 5-HT3 receptor antagonist VI. Product Availability Tablet: 90 mg
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   CLINICAL POLICY Rolapitant VII.