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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:020
Effective Date: 07/23/2019
Original Policy Date:02/20/1998
Last Review Date:02/12/2019
Date Published to Web: 04/24/2019
Subject:
Topotecan Hydrochloride (Hycamtin) Injection

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

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Topotecan hydrochloride is currently marketed as Hycamtin by GlaxoSmithKline Pharmaceuticals. Hycamtin is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. It is available as a sterile lyophilized, powder available for intravenous administration.

[INFORMATIONAL NOTE: The FDA-approved Hycamtin (topotecan hydrochloride) package insert has the following BLACK BOX WARNING:
Hycamtin can cause severe myelosuppression. Administer only to patients with baseline neutrophil counts of greater than or equal to 1,500 cells/mm3 and platelet counts greater than or equal to 100,000 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection and death, frequent peripheral blood cell counts should be performed on all patients receiving Hycamtin.]

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

1. Topotecan hydrochloride (Hycamtin) injection is medically necessary for the following FDA-approved indications:

    A. Treatment of members with metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.
      [INFORMATIONAL NOTE: The FDA approved recommended dose of Hycamtin is 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on day 1 of a 21-day course. A minimum of four courses is recommended because median time to response in three clinical trials was 9 to 12 weeks.

      In the event of severe neutropenia during any course, the dose should be reduced by 0.25 mg/m2 (to 1.25 mg/m2) for subsequent courses. Doses should be similarly reduced if the platelet count falls below 25,000 cells/mm3. Alternatively, in the event of severe neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from day 6 of the course (24 hours after completion of topotecan administration).]

    B. Treatment of members with small cell lung cancer platinum-sensitive disease after failure of first-line chemotherapy (progressed at least 60 days after initiation of first-line chemotherapy).
      [INFORMATIONAL NOTE: The FDA approved recommended dose of Hycamtin for ovarian and small cell lung cancer is 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on day 1 of a 21-day course. A minimum of four courses is recommended. The median time to response in three ovarian clinical trials was 9 to 12 weeks, and median time to response in 4 small lung cancer trials was 5 to 7 weeks.
      In clinical studies submitted to support approval, sensitive disease was defined as disease responding to chemotherapy but subsequently progressing at least 60 days (in the Phase 3 study) or at least 90 days (in the Phase 2 studies) after chemotherapy.

      In the event of severe neutropenia during any course, the dose should be reduced by 0.25 mg/m2 (to 1.25 mg/m2) for subsequent courses. Doses should be similarly reduced if the platelet count falls below 25,000 cells/mm3. Alternatively, in the event of severe neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from day 6 of the course (24 hours after completion of topotecan administration).]
    C. Combination treatment with cisplatin for members with stage IV-B, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy.
      [INFORMATIONAL NOTE: According to the FDA approved package insert, the recommended dose of Hycamtin for cervical cancer is 0.75 mg/m2 by intravenous infusion over 30 minutes daily on days 1, 2, and 3; followed by cisplatin 50 mg/m2 infusion on day 1 repeated every 21 days (a 21-day course). In the event of severe febrile neutropenia (defined as <1000 cells/mm3 with a temperature of 38°C or 100.4°F) or if platelet count falls below 25,000 cells/mm3, the dose of Hycamtin should be reduced by 20% to 0.60 mg/m2 for subsequent courses. Alternatively, in the event of severe febrile neutropenia, G-CSF may be administered following the subsequent course (before resorting to dose reduction) starting from day 4 of the course (24 hours after completion of administration of Hycamtin). If febrile neutropenia occurs despite the use of G-CSF, the dose of Hycamtin should be reduced by another 20% to 0.45 mg/m2 for subsequent courses.]

2. Topotecan hydrochloride (Hycamtin) injection is medically necessary for the following off-label uses:
    A. Central Nervous System Cancers – Leptomeningeal Metastases: Intracerebrospinal fluid (CSF) treatment for leptomeningeal metastases
          • Following radiation therapy as primary treatment for patients with normal CSF flow; OR
          • As maintenance therapy for patients with negative CSF cytology; OR
          • For clinically stable or improving patients with positive CSF cytology without progression; OR
          • Treatment in patients with positive CSF cytology
    B. Metastatic Central Nervous System Cancers:
          • Limited Brain Metastases
            · Single-agent treatment for recurrent brain metastases in patients with small cell lung cancer and stable systemic disease or reasonable systemic treatment options
          • Extensive Brain Metastases
            · Single-agent treatment for recurrent brain metastases in patients with small cell lung cancer and stable systemic disease or reasonable systemic treatment options
      C. Small Cell Lung Cancer
              Subsequent systemic therapy for patients with performance status 0-2 as a single agent for
                Relapse within 6 months following complete or partial response or stable disease with initial treatment
                Primary progressive disease
      [INFORMATIONAL NOTE: The Eastern Cooperative Oncology Group (ECOG) scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.
      ECOG PERFORMANCE STATUS
      0 - Fully active, able to carry on all pre-disease performance without restriction
      1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
      2 - Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
      3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
      4 - Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
      5 - Dead ]

      D. Rhabdomyosarcoma
        • Single-agent or combination therapy with cyclophosphamide for nonpleomorphic rhabdomyosarcoma
      E. Endometrial Carcinoma
        • Primary treatment as a single agent
            • May be considered for select patients with disease limited to the uterus that is not suitable for pimary surgery
            • Preoperatively for patients presenting with ascites and/or disease in the omentum, lumph notes (including inguinal nodes), ovaries, or peritoneum
            • With or without sequential EBR
            • With or without sequential EBRT and/or brachytherapy for extrauterine pelvic disease
            • With or without EBRT and/or hormonal therapy for extra-abdominal or liver disease
        • Adjuvant treatment as single-agent:
            • With or without vaginal brachytherapy for stage 1A disease
            • Sequential EBRT with or without vaginal brachytherapy for stage IB-IV disease
        • Adjuvant treatment for surgically staged patients as a single agent:
            • With sequential EBRT with or without vaginal brachytherapy for stage III disease
            • With or without sequential EBRT and vaginal brachytherapy for stage IV disease
            • With sequential ERBT with or without vaginal brachytherapy in patients with stage II disease and histologic grade 3 tumors
        • Single agent
            • For disseminated metastases that have progressed on hormonal therapy
            • With or without sequential palliative EBRT for symptomatic, grade 2-3, or large-volume disseminated metastases or for local/regional recurrence in patients with gross upper abdominal residual disease
            • With sequential EBRT with or without brachytherapy for local/regional recurrence in patients with disease confined to the vagina or in pelvic lymph nodes
            • With sequential EBRT for local/regional recurrence in patients with disease in para-aortic or common iliac lymph nodes
            • With or without sequential tumor-directed EBRT for local/regional recurrence in patients with microscopic residual upper abdominal or peritoneal disease
            • For local/regional recurrence in patients who have received prior EBRT to site of recurrence
      F. Ewing Sarcoma
        · Used in combination with cyclophosphamide with or without vincristine
            • with or without radiation therapy for relapse
            • for progressive disease following primary treatment
            • as second-line therapy for metastatic disease
      G. Osteosarcoma
        · Second-line therapy for relapsed/refractory or metastatic disease in combination with cyclophosphamide
      H. Primary central nervous system lymphoma
        · Treatment as a single agent for relapsed or refractory disease
            • may be considered in patients who received prior whole brain radiation therapy
            • in patients who received a prior high-dose methotrexate-based regimen without prior radiation therapy (RT) after previous response with long duration (≥12 months) to prior regimen
            • in combination with whole brain RT or involved field RT in patients who received a prior high-dose methotrexate-based regimen without prior RT after no response or short response duration (<12 months) to prior regimen
            • in patients who received prior high-dose chemotherapy with stem cell rescue after previous response with long duration (≥12 months)
      I. Cervical Cancer
        · First-line therapy, or second-line therapy as clinically appropriate (if not used previously as first-line) in combination with paclitaxel with or without bevacizumab (preferred regimens), or in combination with cisplatin for
            • local/regional recurrence
            • stage IVB or distant metastases
      J. Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer - Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer
        • preferred therapy, if platinum-resistant, for persistent disease or recurrence
            • as a single agent
            • in combination with bevacizumab
3. The use of topotecan hydrochloride (Hycamtin) injection is considered investigational in other conditions including, but not limited to, the following:
      • Breast cancer
      • Pancreatic cancer
      • Prostate cancer
      • Stomach cancer
      • Colorectal cancer
      • Germ cell tumor
      • Head and neck cancer
      • Hepatoblastoma
      • Malignant glioma
      • Fibrosarcoma
      • Multiple myeloma
      • Myelodysplastic syndrome
      • Nephroblastoma
      • Neuroblastoma
      • Primitive neuroectodermal tumor
      • Renal cell carcinoma
      • Urothelial carcinoma
      • Neuroendocrine carcinoma
      • Retinoblastoma

Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for Topotecan Hydrochloride (Hycamtin) Injection. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.
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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Topotecan Hydrochloride (Hycamtin) Injection
Hycamtin (Topotecan Hydrochloride) Injection

References:
1. 2004 Physicians' Desk Reference. 58th Edition. Medical Economics Publishing Company.

2. Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, a New Active Drug in the Second-Line Treatment of Small-Cell Lung Cancer: A Phase II Study in Patients With Refractory and Sensitive Disease. J Clin Oncol. May 1997;15(5):2090-2096.

3. Beran M, Estey E, O'Brien SM, et al. Results of topotecan single-agent therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 1998; 31(5-6):521-531.

4. Beran M, Kantarjian H, O'Brien S, et al. Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 1996; 88(7):2473-2479.

5. Bunn PA Jr. The treatment of non-small cell lung cancer: current perspectives and controversies, future directions. Semin Oncol 1994; 21(suppl 6):49-59.

6. Green MR. New directions for chemotherapy in non-small-cell lung cancer. Chest 1993; 103(suppl):370S-372S.

7. Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. J Clin Oncol 1997; 15:2090-2096.

8. Edelman MJ, Gandara DR. Promising new agents in the treatment of non-small cell lung cancer. Cancer Chemother Pharmacol 1996; 37:385-393.

9. Feigal EG, Christian M, Cheson B, et al. New chemotherapeutic agents in non-small-cell lung cancer. Semin Oncol 1993; 20:185-201.

10. Herben VMM, ten Bokkel Huinink WW, Schot ME, et al. Continuous infusion of low-dose topotecan: pharmacokinetics and pharmacodynamics during a phase II study in patients with small cell lung cancer. Anticancer Drugs 1998; 9:411-418.

11. Micromedex Healthcare Series United States Pharmacopeia Drug Information (USPDI) for the Health Care Professional [database online]. Thomson Healthcare, Inc; 1974-2010. Available at: http://www.thomsonhc.com (accessed 02/23/2013 02/28/2014).

12. American Society of Health-Systems Pharmacists. American Hospital Formulary Service (AHFS) Drug Information 2009.

13. Hycamtin® (topotecan hydrochloride) for injection [prescribing information]. GlaxoSmithKline. Research Triangle Park, NC. Sept 2018. Accessed January 30,2019.

14. Smith SM, Johnson JL, Niedzwiecki DE, et al. Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin’s lymphoma: results of CALGB 59906. Leukemia and Lymphoma 2006;47(8):1511-7.

15. Simon T, Langler A, Berthold F, et al. Topotecan and etoposide in the treatment of relapsed high-risk neuroblastoma: results of a phase 2 trial. Journal of Pediatric Hematology/Oncology 2007;29(2):101-6.

16. Fischer L, Thiel E, Klasen HA, et al. Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Annals of Oncology 2006;17(7):1141-5.

17. Toptecan;Toptecan hydrochloride. National Comprehensive Cancer Network: Drugs and Biologics Compendium. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/HTML/Topotecan;%20Topotecan%20hydrochloride.asp [Accessed 2/1/2017 ]

18. Topotecan. Clinical Pharmacology. 2009. Available at: https://clinicalpharmacology.com/default.aspx [Accessed 02/28/2014].

19. Fiorica JV, Blessing JA, Puneky LV, et al. A Phase II evaluation of weekly topotecan as a single agent second line therapy in persistent or recurrent carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2009 Nov;115(2):285-9.

20. Kurata T, Kashii T, Takeda K, et al. A phase I study of topotecan plus carboplatin for relapsed SCLC: WJTOG trial. J Thorac Oncol. 2009;4(5):644-8.

21. Meier W, du Bois A, Reuss A, et al. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy. A prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009;114(2):199-205.

22. Kang H, Kim TJ, Lee YY, et al. Topotecan combined with carboplatin in recurrent epithelial ovarian cancer: results of a single-institutional phase II study. Gynecol Oncol. 2009 Aug;114(2):210-4.

23. Walterhouse DO, Lyden ER, Breitfeld PP, et al. Efficacy of topotecan and cyclophosphamide given in a phase II window trial in children with newly diagnosed metastatic rhabdomyosarcoma: a Children's Oncology Group study. J Clin Oncol. 2004;22(8):1398-403.

24. Olsen IH, Kniqqe U, Federspiel B, et al. Topotecan monotherapy in heavily pretreated patients with progressive advanced stage neuroendocrine carcinomas. J Cancer. 2014 1;5(8):628-32.

25. Schaiquevich P, Carcaboso AM, Buitrago E. Ocular pharmacology of topotecan and its activity in retinoblastoma. Retina. 2014;34(9):1719-27 and Taich P, Ceciliano A, Buitrago E. Clinical pharmacokinetics of intra-arterial melphalan and topotecan combination in patients with retinoblastoma. Ophthalmology. 2014;121(4):889-97.)

26. Uterine Neoplasms Version 1.2018 NCCN Clinical practice guidelines in oncology. Natational Comprehensive Cancer Network. Accessed February 2018.

27. Small Cell Lung Cancer Version 2.2018 NCCN Clinical practice guidelines in oncology. Natational Comprehensive Cancer Network. Accessed February 2018.

28. Central Nervous System Cancers Version 1.2017 NCCN Clinical practice guidelines in oncology. Natational Comprehensive Cancer Network. Accessed February 2018.

29. Topotecan hydrochloride. National Comprehensive Cancer Network: Drugs and Biologics Compendium. [Available at https://www.nccn.org/professionals/drug_compendium/content/ (accessed 1/2019).]

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

    J9350
    J9351

* CPT only copyright 2019 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

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