BlueCross BlueShield of Tennessee Medical Policy Manual

Bevacizumab Products for the Treatment of Neoplastic Disease (Avastin®, bevacizumab-awwb [Mvasi®] and bevacizumab-bvzr [Zirabev™])

NDC CODE(S)

50242-0060-XX AVASTIN 100 MG/4ML Solution (GENENTECH)

50242-0060-XX AVASTIN 25MG/ML Solution (GENENTECH)

50242-0061-XX AVASTIN 25MG/ML Solution (GENENTECH)

55513-0206-XX MVASI 25MG/ML (4ML) Solution (AMGEN)

55513-0207-XX MVASI 25MG/ML (16ML) Solution (AMGEN)

00069-0315-XX ZIRABEV 100 MG/4ML Solution (PFIZER U.S.)

00069-0342- XX ZIRABEV 400 MG/16ML Solution (PFIZER U.S.)

DESCRIPTION

Bevacizumab is a recombinant humanized monoclonal IgG1 antibody which binds to human vascular endothelial growth factor (VEGF).  VEGF normally interacts with receptors (Flt-1 and KDR) on the surface of endothelial cells and leads to endothelial cell proliferation and new blood vessel formation.  By binding to VEGF, bevacizumab halts interaction with these receptors, resulting in reduction of microvascular growth and inhibition of metastatic disease progression.

Biosimilar products are biological products that are highly similar to an existing FDA-approved innovator product and have no clinically meaningful differences from the innovator product.  The differences in the biosimilars must be proven to be in the clinically inactive components of the biosimilars, e.g., stabilizers or buffers. 

At present, two products have been approved as biosimilar to bevacizumab, bevacizumab-awwb (Mvasi®) and bevacizumab-bvzr (Zirabev).  Their clinical use mirrors that of bevacizumab.

Note: This policy does not address the use of bevacizumab products for the treatment of disorders of the eye.  Preauthorization is not required when used in the treatment of eye disorders.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Universal Criteria

Colorectal Cancer (CRC)

Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

*  Note: If there is insufficient tissue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.

Cervical Cancer

Breast Cancer

Renal Cell Carcinoma (RCC)

Central Nervous System (CNS) Cancer

Ovarian Cancer

Soft Tissue Sarcoma

Endometrial Carcinoma (Uterine Neoplasms)

Malignant Pleural Mesothelioma (MPM)*

Vulvar Cancer

Small Bowel Adenocarcinoma

Hepatocellular Carcinoma (HCC)

Neurofibromatosis

Genomic Aberration Targeted Therapies

(not all inclusive, refer to guidelines for appropriate use)

  • Sensitizing EGFR mutation-positive tumors

    • Afatinib

    • Dacomitinib

    • Erlotinib

    • Gefitinib

    • Osimertinib

  • ALK rearrangement-positive tumors

    • Alectinib

    • Brigatinib

    • Ceritinib

    • Crizotinib

    • Lorlatinib

 

  • ROS1 rearrangement-positive tumors

    • Ceritinib

    • Crizotinib

    • Entrectinib

  • BRAF V600E-mutation positive tumors

    • Dabrafenib ± Trametinib

    • Vemurafenib

 

  • NTRK Gene Fusion positive tumors

    • Entrectinib

    • Larotrectinib

  • PD-1 / PD-L1 expression-positive tumors (> 1%)

    • Atezolizumab

    • Nivolumab ± ipilimumab

    • Pembrolizumab

 

  • MET Exon-14 skipping mutations

    • Capmatinib

    • Crizotinib

  • RET rearrangement-positive tumors

    • Cabozantinib

    • Selpercatinib

    • Vandetanib

 

RENEWAL CRITERIA

CNS Cancers – symptom management (short-course therapy):

Colorectal Cancer (after first-line bevacizumab-containing regimen):

Malignant Mesothelioma (maintenance therapy):

Ovarian Cancer (initial/adjuvant therapy):

Ovarian Cancer (maintenance therapy):

Non-Squamous Non-Small Cell Lung Cancer (continuation therapy in combination with erlotinib):

DOSAGE/ADMINISTRATION

INDICATION

DOSE

CRC

Administer 5 to 10 mg/kg intravenously every 2 weeks OR 7.5 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

Small Bowel Adenocarcinoma

Administer 5 mg/kg intravenously every 2 weeks OR 7.5 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

NSCLC & Cervical Cancer

Administer 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

CNS Cancers

o    For disease treatment: Administer 10 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

o    For symptom management: Administer 5 to 10 mg/kg intravenously every 2 weeks up to 12 weeks duration.

RCC

Administer 10 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

MPM

Administer 15 mg/kg intravenously every 3 weeks in combination with chemotherapy for up to 6 cycles. May follow with maintenance therapy with single-agent bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

Ovarian Cancer

Initial/Adjuvant Therapy

Administer 15 mg/kg intravenously every 3 weeks in combination with

carboplatin and paclitaxel for up to 6 cycles, followed by single agent

bevacizumab 15 mg/kg every 3 weeks for up to a total of 22 cycles or until disease

progression or unacceptable toxicity, whichever occurs earlier.

Persistent/Recurrent Disease

Platinum-sensitive disease:

Administer 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

Platinum-resistant disease:

Administer 10 mg/kg intravenously every 2 weeks OR 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

All Other Treatment Settings

Administer 5 to 10 mg/kg intravenously every 2 weeks OR 7.5 to 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

HCC

Administer 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

All Other Oncology Indications

Administer 5 to 10 mg/kg intravenously every 2 weeks OR 7.5 to 15 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity.

LENGTH OF AUTHORIZATION

For initial/adjuvant treatment of ovarian cancer, coverage will be provided for up to a maximum of 22 cycles (66 weeks).

DOSAGE LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

Oncology indications

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.     Avastin [package insert]. South San Francisco, CA; Genentech; December 2020. Accessed January 2021.

2.     Mvasi [package insert]. Thousand Oaks, CA; Amgen, Inc.; June 2019. Accessed January 2021.

3.     Zirabev [package insert]. New York, NY; Pfizer, Inc.; January 2020. Accessed January 2021.

4.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) bevacizumab. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

5.     Ceresoli GL, Zucali PA, Mencoboni M, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer. 2013 Aug 6; 109(3): 552–558

6.     Delishaj D, Ursino S, Pasqualetti F, et al. Bevacizumab for the Treatment of Radiation-Induced Cerebral Necrosis: A Systematic Review of the Literature. J Clin Med Res. 2017 Apr; 9(4): 273–280.

7.     Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.

8.     Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf

9.     Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.

10.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer 2.2021. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2021.

11.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer 1.2020. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2021.

12.  Thatcher N, Goldschmidt JH, Thomas M, et al. Efficacy and safety of biosimilar ABP 215 compared with bevacizumab in patients with advanced nonsquamous non-small cell lung cancer (MAPLE): a randomized, double-blind, phase III study. Clin Cancer Res. 2019;25:2088-2095.

13.  Reinmuth N, Bryl M, Bondarenko I, et al. PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin®), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study. BioDrugs. 2019 Oct;33(5):555-570. doi: 10.1007/s40259-019-00363-4.

14.  Cheng AL, Qin S, Ikeda M, et al. LBA3-IMBrave150: Efficacy and safety results from a ph III study evaluating atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (Sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC). Ann Oncol. 2019 Nov;30 Suppl 9:ix186-ix187.

15.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers 5.2020. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2021.

16.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Small Bowel Adenocarcinoma 2.2020. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2021.

17.  Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42.

18.  Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25(12):1539-1544.

19.  Chen HX, Mooney M, Boron M, et al. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol. 2006;24(21):3354-3360. doi:10.1200/JCO.2005.05.1573.

20.  Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013 Jan;14(1):29-37.

21.  de Gramont A, Van Cutsem E, Schmoll HJ, et al. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012;13(12):1225-1233. doi:10.1016/S1470-2045(12)70509-0.

22.  Allegra CJ, Yothers G, O'Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011;29(1):11-16. doi:10.1200/JCO.2010.30.0855.

23.  Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50.

24.  Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009 Mar 10;27(8):1227-34.

25.  Wick W, Gorlia T, Bendszus M, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med 2017; 377:1954-1963.

26.  Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40.

27.  Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370(9605):2103-2111. doi:10.1016/S0140-6736(07)61904-7.

28.  Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390(10103):1654-1663. doi:10.1016/S0140-6736(17)31607-0.

29.  Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83.

30.  Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. Journal of Clinical Oncology 2014 32:13, 1302-1308.

31.  Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30(17):2039–2045.

32.  Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18(6):779–791.

33.  Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60.

34.  Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013;24(1):257-263.

35.  Lorusso D, Ferrandina G, Colombo N, et al. Randomized phase II trial of carboplatin-paclitaxel (CP) compared to carboplatin-paclitaxel-bevacizumab (CP-B) in advanced (stage III-IV) or recurrent endometrial cancer: The MITO END-2 trial. Journal of Clinical Oncology 2015 33:15_suppl, 5502-5502.

36.  Miller K, Wang M, Gralow Jet al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76.

37.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Malignant Pleural Mesothelioma 1.2021. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed January 2021.

38.  Zalcman G, Mazieres J, Margery J, et al; French Cooperative Thoracic Intergroup (IFCT). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Apr 2;387(10026):1405-1414.

39.  Lexi-Comp Online. (2021). AHFS DI. Bevacizumab. Retrieved January 21, 2021 from Lexi-Comp Online with AHFS.

40.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2021, January). Bevacizumab. Retrieved January 21, 2021 from MICRODEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  2/1/2005

MOST RECENT REVIEW DATE:    7/31/2021

ID_MRx

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