HYCAMTIN, Topotecan HCl Form

Topotecan (Hycamtin®) is a topoisomerase inhibitor. FDA Approved Indication(s) Hycamtin capsules are indicated for the treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy. Hycamtin for injection is indicated: • As a single agent for the treatment of patients with metastatic carcinoma of the ovary after disease progression on or after initial or subsequent chemotherapy; • As a single agent for the treatment of patients with small cell lung cancer with platinum- • sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy; In combination with cisplatin for the treatment of patients with Stage IV-B, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment. 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 Hycamtin is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Ovarian Cancer (must meet all):

1. Diagnosis of ovarian cancer (including epithelial carcinoma, mucinous carcinoma, clear cell carcinoma, endometrioid carcinoma, low-grade serious carcinoma, and carcinosarcoma), fallopian tube cancer, or primary peritoneal cancer;
2. Request is for topotecan for injection;
   3. Prescribed by or in consultation with an oncologist;
   4. Age ≥ 18 years;
   5. Disease progression on or after initial or subsequent chemotherapy;
   6. Prescribed in one of the following ways (a or b): a. As a single agent; b. In combination with bevacizumab or sorafenib (off-label);

3. Request meets one of the following (a or b):* a. Dose does not exceed 1.5 mg/m2 per day for 5 consecutive days every 21 days; Page 1 of 8

   CLINICAL POLICY Topotecan 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 – 6 months or to the member’s renewal date, whichever is longer B. Small Cell Lung Cancer (must meet all):

   1. Diagnosis of small cell lung cancer;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member has received prior chemotherapy;
   5. Request meets one of the following (a or b): a. Dose does not exceed the following: Injection: 1.5 mg/m2 per day IV for 5 consecutive days every 21 days; i. ii. Capsule: 2.3 mg/m2 per day orally for 5 consecutive days every 21 days; 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 – 6 months or to the member’s renewal date, whichever is longer (injection); 12 months or duration of request, whichever is less (capsule) C. Cervical Cancer (must meet all):
   6. Diagnosis of cervical cancer;
   7. Request is for topotecan for injection;
   8. Prescribed by or in consultation with an oncologist;
   9. Age ≥ 18 years;
   10. Prescribed in one of the following ways (a or b): a. In combination with cisplatin or paclitaxel; b. As a single agent as second-line or subsequent therapy;
4. Request meets one of the following (a or b): a. Dose does not exceed 0.75 mg/m2 per day on days 1-3 every 21 days; 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 – 6 months or to the member’s renewal date, whichever is longer
   D. NCCN Recommended Uses (off-label) (must meet all):

5. Prescribed for one of the following diagnoses: a. Request is for topotecan for injection: i. Ewing sarcoma, and prescribed as a second line therapy in combination with cyclophosphamide; Page 2 of 8

   CLINICAL POLICY Topotecan ii. Osteosarcoma, and prescribed as a second line therapy in combination with cyclophosphamide; iii. Leptomeningeal metastases, and route of administration is intrathecal;
   iv. Non-pleomorphic rhabdomyosarcoma, and prescribed as a single agent or in combination with cyclophosphamide; v. Endometrial carcinoma as second-line or subsequent therapy, and prescribed as a single agent; b. Request is for topotecan for injection or topotecan capsules: i. Merkel cell carcinoma, and member has contraindications to checkpoint immunotherapy (e.g., avelumab, pembrolizumab, nivolumab);

6. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. 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/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer (injection); 12 months or duration of request, whichever is less (capsule). E. 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. II. Continued Therapy A. All Indications in Section I (must meet all):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Hycamtin for a covered indication and has received this medication for at least 30 days;

10. Member is responding positively to therapy; Page 3 of 8

    CLINICAL POLICY Topotecan

11. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed the following (i, ii, or iii): i. Ovarian cancer: 1.5 mg/m2 per day IV for 5 consecutive days every 21 days; ii. Small cell lung cancer: 1.5 mg/m2 per day IV or 2.3 mg/m2/day orally for 5 consecutive days repeated every 21 days; iii. Cervical cancer: 0.75 mg/m2 per day IV on days 1-3 every 21 days; 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 – 6 months or to the member’s renewal date, whichever is longer (injection); 12 months or duration of request, whichever is less (capsule) B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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 policy – 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 FDA: Food and Drug Administration NCCN: National Comprehensive Cancer Network Page 4 of 8

    CLINICAL POLICY Topotecan 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 Varies Varies Varies Varies Examples of therapies for ovarian cancer: paclitaxel, carboplatin, cisplatin, doxorubicin, ifosfamide, bevacizumab Examples of therapies for small cell lung cancer: cisplatin, carboplatin, etoposide, atezolizumab, durvalumab, irinotecan Examples of therapies for cervical cancer: cisplatin, carboplatin, pembrolizumab, bevacizumab, nivolumab, paclitaxel, docetaxel, fluorouracil, gemcitabine, ifosfamide, irinotecan, mitomycin, pemetrexed, vinorelbine, tisotumab vedotin-tftv Examples of therapies for Ewing sarcoma and osteosarcoma: pembrolizumab, dasatinib, pazopanib, ivosidenib 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. *Examples are not all-inclusive and may be used alone or in various combination regimens; refer to NCCN guidelines for additional detail Varies Varies Varies Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of severe hypersensitivity reactions to topotecan • Boxed warning(s): myelosuppression V. Dosage and Administration Indication Dosing Regimen Ovarian cancer IV infusion dosage: 1.5 mg/m2 IV over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course IV infusion dosage: 1.5 mg/m2 IV over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course Small cell lung cancer Cervical cancer Oral dosage: 2.3 mg/m2/day orally once daily for 5 consecutive days repeated every 21 days IV infusion dosage: 0.75 mg/m2 IV over 30 minutes daily on Days 1, 2, and 3 repeated every 21 days in combination with cisplatin 50 mg/m2 on Day 1 Page 5 of 8 Maximum Dose 4 mg/dose if IV infusion, otherwise refer to regimen 4 mg/dose if IV infusion, otherwise refer to regimen
    4 mg/dose if IV infusion, otherwise refer to regimen

    CLINICAL POLICY Topotecan VI. Product Availability
    • Capsules: 0.25 mg, 1 mg • Lyophilized powder in single use vial for injection: 4-mg (free base)
    VII.