VALSTAR, Valrubicin Form

Valrubicin (Valstar®) is an anthracycline topoisomerase inhibitor. FDA Approved Indication(s) Valstar is indicated for the intravesical therapy of bacillus Calmette-Guerin (BCG)-refractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. 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 Valstar is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Bladder Cancer (must meet all):

1. Diagnosis of recurrent or persistent CIS of the urinary bladder;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a or b): a. Failure of intravesical BCG treatment, unless contraindicated or clinically significant adverse effects are experienced;
      b. Adjuvant intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) in the event of a BCG shortage (see Appendix D for information on BCG shortage); Prior authorization may be required for BCG immunotherapy
2. Request meets one of the following (a or b): a. Dose does not exceed 800 mg per week for a total of 6 doses; 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: 6 weeks (6 doses) B. Other diagnoses/indications (must meet 1 or 2):

3. 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 Valrubicin 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

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: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Bladder Cancer (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Valstar for a covered indication and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   3. Member has not yet received a total of 6 doses;
   4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 800 mg per week; 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: Up to a total of 6 weeks (up to a total of 6 doses) 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. Page 2 of 7

   CLINICAL POLICY Valrubicin 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 BCG: bacillus Calmette-Guerin
   CIS: carcinoma in situ FDA: Food and Drug Administration NMIBC: non-muscle-invasive bladder cancer Dose Limit/ Maximum Dose Undetermined 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 BCG 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. 81 mg intravesically once a week for 6 weeks Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o Perforated bladder or compromised bladder mucosa o Known hypersensitivity to anthracyclines or polyoxyl castor oil o Concurrent urinary tract infections o Small bladder capacity, i.e., unable to tolerate a 75 mL instillation • Boxed warning(s): none reported Appendix D: General Information • Carcinoma in situ (Tis in TNM staging system) refers to early cancer that has not spread to neighboring tissue. • The American Urological Association (AUA) recommends several management approaches to maintain high quality care for patients with non-muscle-invasive bladder cancer (NMIBC). As always, these recommendations are subject to physician judgment in individual cases:
   o BCG should not be used for patients with low-risk disease. o Intravesical chemotherapy should be used as the first-line option for patients with intermediate-risk NMIBC. Patients with recurrent/multifocal low-grade Ta lesions who require intravesical therapy should receive intravesical chemotherapy such as mitomycin, gemcitabine, epirubicin, or docetaxel instead of BCG. o If BCG would be administered as second-line therapy for patients with intermediate- risk NMIBC, an alternative intravesical chemotherapy should be used rather than BCG in the setting of this BCG shortage. Page 3 of 7

   CLINICAL POLICY Valrubicin o For patients with high-risk NMIBC, high-grade T1 and CIS patients receiving induction therapy, they should be prioritized for use of full-strength BCG. If not available, these patients and other high-risk patients may be given a reduced 1/2 to 1/3 dose, if feasible. o If supply exists for maintenance therapy for patients with NMIBC, limit BCG dose to one year. o In the event of BCG supply shortage, maintenance therapy should not be given and BCG naïve patients with high-risk disease should be prioritized for induction BCG. o If BCG is not available, alternatives to BCG such as gemcitabine, epirubicin, docetaxel, valrubicin, mitomycin, or sequential gemcitabine/docetaxel or gemcitabine/mitomycin may also be considered with an induction and possible maintenance regimen. o Patients with high-risk features (i.e., high-grade T1 with additional risk factors such as concomitant CIS, lymphovascular invasion, prostatic urethral involvement or variant histology) who are not willing to take any potential oncologic risks with alternative intravesical agents, should be offered initial radical cystectomy, if they are surgical candidates. • The NCCN guidance in the event of a BCG shortage is generally in accordance with AUA stance. They advise BCG should be prioritized for induction of high-risk patients NMIBC (e.g., high-grade T1 and CIS) and that, if feasible, the dose of BCG may be split (1/3 or 1/2 dose) so that multiple patients may be treated with a single vial in the event of a shortage. o If BCG is unavailable, the NCCN recommends the following alternatives: Intravesical chemotherapy agents as first-line and subsequent therapy (e.g.,  gemcitabine, mitomycin, epirubicin, valrubicin, docetaxel, sequential gemcitabine/docetaxel, gemcitabine/mitomycin);  Initial radical cystectomy if patient is a surgical candidate. __

   1. National Comprehensive Cancer Network Guidelines. Bladder Cancer Version 3.2023. Available at https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed July 11, 2023.
   2. American Urological Association. BCG Shortage Info. Feb 2019. Available at: https://www.auanet.org/about-us/bcg-shortage-info. Accessed July 11, 2023. V. Dosage and Administration
      Indication Bladder CIS Dosing Regimen 800 mg intravesically once every week for 6 weeks Maximum Dose 800 mg/dose VI. Product Availability
      Single-use vials: 200 mg/5 mL VII.