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Bevacizumab: Avastin®; Mvasi™; Zirabev™ (Intravenous)

Policy Number: VP-0014

Last Review Date: 06/01/2021

Date of Origin: 10/17/2008

Dates Reviewed: 06/2009, 12/2009, 03/2010, 06/2010, 09/2010, 12/2010, 02/2011, 03/2011, 06/2011, 09/2011, 12/2011, 03/2011, 06/2012, 09/2012, 12/2012, 02/2013, 03/2013, 06/2013, 08/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 12/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020, 03/2021, 06/2021

FOR PEEHIP Members Only -Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

I. Length of Authorization 6

Coverage will be provided for six months and may be renewed (unless otherwise specified).

  • For CNS cancers (symptom management), coverage will be provided for 12 weeks and may NOT be renewed.

II. Dosing Limits

  1. Quantity Limit (max daily dose) [NDC Unit]:
  • 100 mg/4 mL vial: 3 vials 21 days
  • 400 mg/16 mL vial: 4 vials per 21 days
  1. Max Units (per dose and over time) [HCPCS Unit]:

Oncology indications (J9035/Q5107/Q5118):

  • Small Bowel Adenocarcinoma/Ampullary Cancer:
    • 60 billable units per 14 days
  • CRC, CNS & RCC:
    • 120 billable units per 14 days
  • All other indications:
    • 170 billable units per 21 days
    • 120 billable units per 14 days

III. Initial Approval Criteria 1-3

Coverage is provided in the following conditions:

  • Zirabev (bevacizumab-bvzr) and Mvasi ( bevacizumab-awwb) are the preferred products. Patient must have tried and had an inadequate response or intolerance to, or a contraindication to Zirabev and Mvasi, attributable to the biosimilar formulation, prior to consideration of a non-preferred bevacizumab product including Avastin (bevacizumab) OR Patient is continuing treatment with a non-preferred bevacizumab product including Avastin; AND
  • Patient is at least 18 years of age; AND

Universal Criteria 1

  • Patient has no recent history of hemoptysis (i.e., the presence of ≥2.5 mL of blood in sputum) OR any grade 3-4 hemorrhage; AND
  • Patient must not have had a surgical procedure within the preceding 28 days or have a surgical wound that has not fully healed; AND

Colorectal Cancer (CRC) † ‡ 1-4,17-22

  • Will not be used as part of adjuvant treatment; AND
    • Patient has metastatic, unresectable, or advanced disease; AND
  • Used as first-line or subsequent therapy in combination with a fluoropyrimidine- (e.g., 5-fluorouracil/5-FU or capecitabine) or irinotecan-based regimen; OR
  • Used in combination with a fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based regimen (if not used first line) as second-line therapy for metastatic disease that has progressed on a first-line bevacizumab containing regimen ; OR
  • Used in combination with trifluridine and tipiracil as subsequent therapy for advanced or metastatic disease after progression on all available regimens

Non-Squamous Non-Small Cell Lung Cancer (NSCLC) 1-4,10,12,13,23,24

  • Used as first-line therapy for recurrent, locally advanced, unresectable, or metastatic disease in combination with carboplatin and paclitaxel ; OR
  • Used for recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease) or mediastinal lymph node recurrence with prior radiation therapy; AND
    • Used as first-line therapy; AND
      • Used for one of the following:
  • EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping mutation, and RET rearrangement negative tumors* and PD-L1 < 1% in patients with PS ≤ 1; OR
  • EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping mutation, and RET rearrangement negative tumors* and PD-L1 ≥ 1% in patients with PS ≤ 2; OR
  • BRAF V600E-mutation, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, or RET rearrangement positive tumors in patients with PS ≤ 1; AND
      • Used in combination with:
  • Pemetrexed and either carboplatin or cisplatin (excluding use in patients with PD-L1 ≥ 1%); OR
  • Atezolizumab, carboplatin, and paclitaxel (excluding use in patients with RET rearrangement positive tumors); OR
    • Used as subsequent therapy in patients with PS ≤ 1; AND
      • Used for one of the following:
  • EGFR, ALK, or ROS1 positive tumors and prior targeted therapy§; OR
  • BRAF V600E-mutation, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, or RET rearrangement positive tumors; OR
  • PD-L1 expression-positive (PD-L1 ≥ 1%) tumors that are EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping mutation, and RET negative* with prior PD-1/PD-L1 inhibitor therapy but no prior platinum-doublet chemotherapy; AND
      • Used in combination with:
            • Carboplatin and paclitaxel; OR
            • Pemetrexed and either carboplatin or cisplatin; OR
            • Atezolizumab, carboplatin, and paclitaxel (excluding use in patients who have received prior PD-1/PD-L1 inhibitor therapy or who have EGFR, ALK, and RET rearrangement positive tumors); OR
  • Used as continuation maintenance therapy (bevacizumab must have been included in patient’s first-line chemotherapy regimen) in patients who achieved a tumor response or stable disease after first-line systemic therapy; AND
      • Used as a single agent; OR
      • Used in combination with pemetrexed following a first-line bevacizumab/pemetrexed/platinum chemotherapy regimen; OR
      • Used in combination with atezolizumab following a first-line atezolizumab/carboplatin/paclitaxel/bevacizumab regimen; OR
  • Used in combination with erlotinib for sensitizing EGFR mutation positive disease; AND
      • Used as first-line therapy; OR
      • Used as continuation of therapy following disease progression on erlotinib with bevacizumab for asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited metastases

* 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 † ‡ 1-4,28

  • Patient has persistent, recurrent, or metastatic disease; AND
  • Used in combination with paclitaxel AND either cisplatin, carboplatin, or topotecan

Breast Cancer ‡ 4

  • Patient has recurrent unresectable or metastatic disease; AND
  • Patient has a high tumor burden, rapidly progressive disease, and visceral crisis; AND
  • Used in combination with paclitaxel; AND
  • Patient has human epidermal growth factor receptor 2 (HER2)-negative disease; AND
  • Disease is hormone receptor-negative; OR
  • Disease is hormone receptor-positive with visceral crisis or refractory to endocrine therapy

Renal Cell Carcinoma (RCC) † Ф 1-4,27

  • Used in combination with interferon alfa for metastatic disease ; OR
  • Patient has metastatic or relapsed disease; AND
  • Used as a single agent in patients with non-clear cell histology ; OR
  • Used in combination with everolimus in patients with non-clear cell histology ; OR
  • Used in combination with erlotinib in patients with non-clear cell histology advanced papillary disease including hereditary leiomyomatosis and renal cell cancer (HLRCC)

Central Nervous System (CNS) Cancer  1-4,6,25,26

  • Used for symptom management related to radiation necrosis, poorly controlled vasogenic edema, or mass effect as single-agent short-course therapy; AND
    • Patient has a diagnosis of one of the following other CNS cancers :
    • Infiltrative Supratentorial Astrocytoma/Oligodendroglioma (Low-Grade, WHO Grade II); OR
    • Primary CNS Lymphoma; OR
    • Meningiomas; OR
    • Brain or Spine metastases; OR
    • Medulloblastoma; OR
    • Glioblastoma or Anaplastic Gliomas; OR
    • Intracranial or Spinal Ependymoma (excluding subependymoma); OR
  • Used as a single agent OR in combination with one of the following: carmustine, lomustine, or temozolomide in patients with recurrent Anaplastic Gliomas Ф or recurrent Glioblastoma † ‡; OR
  • Used as a single agent for progressive or recurrent Intracranial or Spinal Ependymoma (excluding subependymoma) after prior radiation therapy ; OR
  • Used as a single agent for patients with surgically inaccessible recurrent or progressive Meningioma when radiation is not possible

Ovarian Cancer † ‡ Ф 1,3,4,11,29-32

  • Patient has malignant stage II-IV sex cord-stromal tumors ; AND
    • Used as single agent therapy for clinically relapsed disease; OR
  • Patient has epithelial ovarian or fallopian tube or primary peritoneal cancer ; AND
    • Patient has persistent or recurrent disease; AND
  • Bevacizumab has not been used previously; AND
  • Patient is not experiencing an immediate biochemical relapse (i.e., rising CA-125 without radiographic evidence of disease); AND
    • Patient has platinum sensitive disease; AND
      • Used as a single agent; OR
      • Used in combination niraparib; OR
      • Used in combination with carboplatin AND either gemcitabine, paclitaxel or PEGylated liposomal-doxorubicin; OR
    • Patient has platinum resistant disease; AND  
      • Used as a single agent; OR
      • Used in combination with one of the following: oral cyclophosphamide, PEGylated liposomal doxorubicin, paclitaxel, or topotecan ; OR
        • Used for rising CA-125 levels or clinical relapse in patients who have received no prior chemotherapy in combination with paclitaxel and carboplatin; OR
    • Used as maintenance therapy; AND
      • Used following primary therapy including bevacizumab; AND
        • Used as a single agent in patients that are BRCA1/2 wild-type or unknown and homologous recombination (HR) proficient or status unknown; OR
        • Used in combination with olaparib; AND
          • Patient is BRCA1/2 wild-type or unknown and HR deficient; OR
          • Patient has a germline or somatic BRCA1/2 mutation; OR
      • Used as a single agent following recurrence therapy with chemotherapy plus bevacizumab for platinum-sensitive disease; OR
      • Used in combination with paclitaxel and carboplatin for stable disease following neoadjuvant therapy as continued maintenance therapy; OR
    • Used as neoadjuvant therapy for endometrioid or serous histology in combination with paclitaxel and carboplatin; AND
  • Patient is a poor surgical candidate or has a low likelihood of optimal cytoreduction; OR
    • Used as adjuvant therapy in combination with paclitaxel and carboplatin; AND
  • Patient has pathologic stage II-IV disease; OR
  • Patient is a poor surgical candidate or has a low likelihood of optimal cytoreduction; AND
    • Patient has endometrioid or serous histology; AND
    • Used after interval debulking surgery (IDS) in patients with a response or stable disease to neoadjuvant therapy

Soft Tissue Sarcoma ‡ 4

  • Used as a single agent for angiosarcoma; OR
  • Used in combination with temozolomide for solitary fibrous tumor

Endometrial Carcinoma (Uterine Neoplasms) ‡ 4

  • Used as single agent therapy for disease that has progressed on prior cytotoxic chemotherapy; OR
  • Used in combination with carboplatin and paclitaxel for advanced and recurrent disease

Malignant Pleural Mesothelioma (MPM)* ‡ 4,37

  • Patient has unresectable disease OR clinical stage IIIB or IV disease, sarcomatoid, or medically inoperable tumors; AND
  • Used in combination with pemetrexed and cisplatin or carboplatin as initial therapy, followed by single-agent maintenance bevacizumab

*peritoneal, pericardial, and tunica vaginalis testis mesothelioma will be evaluated on a case-by-case basis

Vulvar Cancer 4

  • Used in combination with paclitaxel and cisplatin for squamous cell carcinoma; AND
  • Patient has unresectable, locally advanced, metastatic, or recurrent disease

Small Bowel Adenocarcinoma/Advanced Ampullary Cancer 4,16

  • Patient has advanced or metastatic disease; AND
  • Used in combination with a fluoropyrimidine-based regimen; AND
    • Used as initial therapy; OR
    • Used as subsequent therapy after prior initial therapy with nivolumab or pembrolizumab

Hepatocellular Carcinoma (HCC) †Ф 1,4,14,15  

  • Used as first-line therapy in combination with atezolizumab; AND
  • Patient has Child-Pugh Class A disease; AND
  • Patient has unresectable or inoperable (e.g., performance status, comorbidity or with minimal or uncertain extrahepatic-disease) disease, extensive liver tumor burden, or metastatic disease

FDA-labeled indication(s); Compendia recommended indication(s); Ф Orphan Drug

Genomic Aberration/Mutational Driver Targeted Therapies (Note: not all inclusive, refer to guidelines for appropriate use) §

Sensitizing EGFR mutation-positive tumors

  • Afatinib
  • Erlotinib
  • Dacomitinib
  • 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

  • Larotrectinib
  • Entrectinib

PD-1/PD-L1 expression-positive tumors (≥1%)

  • Pembrolizumab
  • Atezolizumab
  • Nivolumab ± ipilimumab

MET Exon-14 skipping mutations

  • Capmatinib
  • Crizotinib
  • Tepotinib

RET rearrangement-positive tumors

  • Selpercatinib
  • Cabozantinib
  • Vandetanib
  • Pralsetinib

IV. Renewal Criteria 1-4

Coverage can be renewed based upon the following criteria:

  • Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
  • Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
  • Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: gastrointestinal perforations and fistulae, surgical/wound healing complications, hemorrhage, arterial and venous thromboembolic events (ATE & VTE), uncontrolled hypertension, posterior reversible encephalopathy syndrome (PRES), nephrotic syndrome, proteinuria, severe infusion reactions, ovarian failure, congestive heart failure (CHF), etc.; AND

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

  • May NOT be renewed

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

  • Refer to Section III for criteria

Malignant Mesothelioma (maintenance therapy):

  • Refer to Section III for criteria

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

  • Refer to Section III for criteria

V. Dosage/Administration 1-3,5,6,16,33-41

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/ Ampullary Cancer

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

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

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.

VI. Billing Code/Availability Information

HCPCS Code:

  • J9035 – Injection, bevacizumab, 10 mg; 1 billable unit = 10 mg
  • Q5107 – Injection, bevacizumab-awwb, biosimilar, (mvasi), 10 mg: 1 billable unit = 10 mg
  • Q5118 – Injection, bevacizumab-bvzr, biosimilar, (zirabev), 10 mg; 1 billable unit = 10 mg

NDC(s):

  • Avastin single-use vial, 100 mg/4 mL solution for injection: 50242-0060-xx
  • Avastin single-use vial, 400 mg/16 mL solution for injection: 50242-0061-xx
  • Mvasi single-use vial, 100 mg/4 mL solution for injection: 55513-0206-xx
  • Mvasi single-use vial, 400 mg/16 mL solution for injection: 55513-0207-xx
  • Zirabev single-use vial, 100 mg/4 mL solution for injection: 00069-0315-xx
  • Zirabev single-use vial, 400 mg/16 mL solution for injection: 00069-0342-xx

VII. References

  1. Avastin [package insert]. South San Francisco, CA; Genentech; January 2021. Accessed May 2021.
  2. Mvasi [package insert]. Thousand Oaks, CA; Amgen, Inc.; April 2021. Accessed May 2021.
  3. Zirabev [package insert]. New York, NY; Pfizer, Inc.; February 2021. Accessed May 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 May 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 4.2021. 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 May 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 1.2021. 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 May 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 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 May 2021.
  16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Small Bowel Adenocarcinoma 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 May 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. doi:10.1093/annonc/mds237.
  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 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 May 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. Park MS, Patel SR, Ludwig JA, et al. Activity of temozolomide and bevacizumab in the treatment of locally advanced, recurrent, and metastatic hemangiopericytoma and malignant solitary fibrous tumor. Cancer. 2011 Nov 1;117(21):4939-47. doi: 10.1002/cncr.26098.
  40. Rose PG, Ali S, Moslemi-Kebria M, et al. Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma. Int J Gynecol Cancer. 2017 Mar;27(3):452-458. doi: 10.1097/IGC.0000000000000891.
  41. Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. doi: 10.1200/JCO.2010.32.6397.
  1. National Government Services, Inc. Local Coverage Article: Billing and Coding: Bevacizumab and biosimilars (A52370). Centers for Medicare & Medicaid Services, Inc. Updated on 04/23/2021 with effective date 05/01/2021. Accessed May 2021.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

 

C17.0

Malignant neoplasm duodenum

 

C17.1

Malignant neoplasm jejunum

 

C17.2

Malignant neoplasm ileum

 

C17.3

Meckel's diverticulum, malignant

 

C17.8

Malignant neoplasm of overlapping sites of small intestines

 

C17.9

Malignant neoplasm of small intestine, unspecified

 

C18.0

Malignant neoplasm of cecum

 

C18.1

Malignant neoplasm of appendix

 

C18.2

Malignant neoplasm of ascending colon

 

C18.3

Malignant neoplasm of hepatic flexure

 

C18.4

Malignant neoplasm of transverse colon

 

C18.5

Malignant neoplasm of splenic flexure

 

C18.6

Malignant neoplasm of descending colon

 

C18.7

Malignant neoplasm of sigmoid colon

 

C18.8

Malignant neoplasm of overlapping sites of large intestines

 

C18.9

Malignant neoplasm of colon, unspecified

 

C19

Malignant neoplasm of rectosigmoid junction

 

C20

Malignant neoplasm of rectum

 

C21.8

Malignant neoplasm of overlapping sites of rectum, anus and anal canal

 

C22.0

Liver cell carcinoma

 

C22.3

Angiosarcoma of the liver

 

C22.8

Malignant neoplasm of liver, primary, unspecified as to type

 

C22.9

Malignant neoplasm of liver, not specified as primary or secondary

 

C24.1

Malignant neoplasm of ampulla of Vater

 

C33

Malignant neoplasm of trachea

 

C34.00

Malignant neoplasm of unspecified main bronchus

 

C34.01

Malignant neoplasm of right main bronchus

 

C34.02

Malignant neoplasm of left main bronchus

 

C34.10

Malignant neoplasm of upper lobe, unspecified bronchus or lung

 

C34.11

Malignant neoplasm of upper lobe, right bronchus or lung

 

C34.12

Malignant neoplasm of upper lobe, left bronchus or lung

 

C34.2

Malignant neoplasm of middle lobe, bronchus or lung

 

C34.30

Malignant neoplasm of lower lobe, unspecified bronchus or lung

 

C34.31

Malignant neoplasm of lower lobe, right bronchus or lung

 

C34.32

Malignant neoplasm of lower lobe, left bronchus or lung

 

C34.80

Malignant neoplasm of overlapping sites of unspecified bronchus or lung

 

C34.81

Malignant neoplasm of overlapping sites of right bronchus and lung

 

C34.82

Malignant neoplasm of overlapping sites of left bronchus and lung

 

C34.90

Malignant neoplasm of unspecified part of unspecified bronchus or lung

 

C34.91

Malignant neoplasm of unspecified part of right bronchus or lung

 

C34.92

Malignant neoplasm of unspecified part of left bronchus or lung

 

C38.4

Malignant neoplasm of pleura

 

C45.0

Mesothelioma of pleura

 

C45.1

Mesothelioma of peritoneum

 

C48.0

Malignant neoplasm of retroperitoneum

 

C48.1

Malignant neoplasm of specified parts of peritoneum

 

C48.2

Malignant neoplasm of peritoneum, unspecified

 

C48.8

Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

 

C49.0

Malignant neoplasm of connective and soft tissue of head, face and neck

 

C49.10

Malignant neoplasm of connective and soft tissue of unspecified upper limb, including shoulder

 

C49.11

Malignant neoplasm of connective and soft tissue of right upper limb including shoulder

 

C49.12

Malignant neoplasm of connective and soft tissue of left upper limb, including shoulder

 

C49.20

Malignant neoplasm of connective and soft tissue of unspecified lower limb, including hip

 

C49.21

Malignant neoplasm of connective and soft tissue of right lower limb, including hip

 

C49.22

Malignant neoplasm of connective and soft tissue of left lower limb, including hip

 

C49.3

Malignant neoplasm of connective and soft tissue of thorax

 

C49.4

Malignant neoplasm of connective and soft tissue of abdomen

 

C49.5

Malignant neoplasm of connective and soft tissue of pelvis

 

C49.6

Malignant neoplasm of connective and soft tissue of trunk, unspecified

 

C49.8

Malignant neoplasm of overlapping sites of connective and soft tissue

 

C49.9

Malignant neoplasm of connective and soft tissue, unspecified

 

C50.011

Malignant neoplasm of nipple and areola, right female breast

 

C50.012

Malignant neoplasm of nipple and areola, left female breast

 

C50.019

Malignant neoplasm of nipple and areola, unspecified female breast

 

C50.021

Malignant neoplasm of nipple and areola, right male breast

 

C50.022

Malignant neoplasm of nipple and areola, left male breast

 

C50.029

Malignant neoplasm of nipple and areola , unspecified male breast

 

C50.111

Malignant neoplasm of central portion of right female breast

 

C50.112

Malignant neoplasm of central portion of left female breast

 

C50.119

Malignant neoplasm of central portion of unspecified female breast

 

C50.121

Malignant neoplasm of central portion of right male breast

 

C50.122

Malignant neoplasm of central portion of left male breast

 

C50.129

Malignant neoplasm of central portion of unspecified male breast

 

C50.211

Malignant neoplasm of upper-inner quadrant of right female breast

 

C50.212

Malignant neoplasm of upper-inner quadrant of left female breast

 

C50.219

Malignant neoplasm of upper-inner quadrant of unspecified  female breast

 

C50.221

Malignant neoplasm of upper-inner quadrant of right male breast

 

C50.222

Malignant neoplasm of upper-inner quadrant of left male breast

 

C50.229

Malignant neoplasm of upper-inner quadrant of unspecified male breast

 

C50.311

Malignant neoplasm of lower-inner quadrant of right female breast

 

C50.312

Malignant neoplasm of lower-inner quadrant of left female breast

 

C50.319

Malignant neoplasm of lower-inner quadrant of unspecified female breast

 

C50.321

Malignant neoplasm of lower-inner quadrant of right male breast

 

C50.322

Malignant neoplasm of lower-inner quadrant of left male breast

 

C50.329

Malignant neoplasm of lower-inner quadrant of unspecified male breast

 

C50.411

Malignant neoplasm of upper-outer quadrant of right female breast

 

C50.412

Malignant neoplasm of upper-outer quadrant of left female breast

 

C50.419

Malignant neoplasm of upper-outer quadrant of unspecified female breast

 

C50.421

Malignant neoplasm of upper-outer quadrant of right male breast

 

C50.422

Malignant neoplasm of upper-outer quadrant of left male breast

 

C50.429

Malignant neoplasm of upper-outer quadrant of unspecified male breast

 

C50.511

Malignant neoplasm of lower-outer quadrant of right female breast

 

C50.512

Malignant neoplasm of lower-outer quadrant of left female breast

 

C50.519

Malignant neoplasm of lower-outer quadrant of unspecified female breast

 

C50.521

Malignant neoplasm of lower-outer quadrant of right male breast

 

C50.522

Malignant neoplasm of lower-outer quadrant of left male breast

 

C50.529

Malignant neoplasm of lower-outer quadrant of unspecified male breast

 

C50.611

Malignant neoplasm of axillary tail of right female breast

 

C50.612

Malignant neoplasm of axillary tail of left female breast

 

C50.619

Malignant neoplasm of axillary tail of unspecified female breast

 

C50.621

Malignant neoplasm of axillary tail of right male breast

 

C50.622

Malignant neoplasm of axillary tail of left male breast

 

C50.629

Malignant neoplasm of axillary tail of unspecified male breast

 

C50.811

Malignant neoplasm of overlapping sites of right female breast

 

C50.812

Malignant neoplasm of overlapping sites of left female breast

 

C50.819

Malignant neoplasm of overlapping sites of unspecified female breast

 

C50.821

Malignant neoplasm of overlapping sites of right male breast

 

C50.822

Malignant neoplasm of overlapping sites of left male breast

 

C50.829

Malignant neoplasm of overlapping sites of unspecified male breast

 

C50.911

Malignant neoplasm of unspecified site of right female breast

 

C50.912

Malignant neoplasm of unspecified site of left female breast

 

C50.919

Malignant neoplasm of unspecified site of unspecified female breast

 

C50.921

Malignant neoplasm of unspecified site of right male breast

 

C50.922

Malignant neoplasm of unspecified site of left male breast

 

C50.929

Malignant neoplasm of unspecified site of unspecified male breast

 

C51.0

Malignant neoplasm of labium majus

 

C51.1

Malignant neoplasm of labium minus

 

C51.2

Malignant neoplasm of clitoris

 

C51.8

Malignant neoplasm of overlapping sites of vulva

 

C51.9

Malignant neoplasm of vulva, unspecified

 

C53.0

Malignant neoplasm of endocervix

 

C53.1

Malignant neoplasm of exocervix

 

C53.8

Malignant neoplasm of overlapping sites of cervix uteri

 

C53.9

Malignant neoplasm of cervix uteri, unspecified

 

C54.0

Malignant neoplasm of isthmus uteri

 

C54.1

Malignant neoplasm of endometrium

 

C54.2

Malignant neoplasm of myometrium

 

C54.3

Malignant neoplasm of fundus uteri

 

C54.8

Malignant neoplasm of overlapping sites of corpus uteri

 

C54.9

Malignant neoplasm of corpus uteri, unspecified

 

C55

Malignant neoplasm of uterus, part unspecified

 

C56.1

Malignant neoplasm of right ovary

 

C56.2

Malignant neoplasm of left ovary

 

C56.9

Malignant neoplasm of unspecified ovary

 

C57.00

Malignant neoplasm of unspecified fallopian tube

 

C57.01

Malignant neoplasm of right fallopian tube

 

C57.02

Malignant neoplasm of left fallopian tube

 

C57.10

Malignant neoplasm of unspecified broad ligament

 

C57.11

Malignant neoplasm of right broad ligament

 

C57.12

Malignant neoplasm of left broad ligament

 

C57.20

Malignant neoplasm of unspecified round ligament

 

C57.21

Malignant neoplasm of right round ligament

 

C57.22

Malignant neoplasm of left round ligament

 

C57.3

Malignant neoplasm of parametrium

 

C57.4

Malignant neoplasm of uterine adnexa, unspecified

 

C57.7

Malignant neoplasm of other specified female genital organs

 

C57.8

Malignant neoplasm of overlapping sites of female genital organs

 

C57.9

Malignant neoplasm of female genital organ, unspecified

 

C64.1

Malignant neoplasm of right kidney, except renal pelvis

 

C64.2

Malignant neoplasm of left kidney, except renal pelvis

 

C64.9

Malignant neoplasm of unspecified kidney, except renal pelvis

 

C65.1

Malignant neoplasm of right renal pelvis

 

C65.2

Malignant neoplasm of left renal pelvis

 

C65.9

Malignant neoplasm of unspecified renal pelvis

 

C70.0

Malignant neoplasm of cerebral meninges

 

C70.1

Malignant neoplasm of spinal meninges

 

C70.9

Malignant neoplasm of meninges, unspecified

 

C71.0

Malignant neoplasm of cerebrum, except lobes and ventricles

 

C71.1

Malignant neoplasm of frontal lobe

 

C71.2

Malignant neoplasm of temporal lobe

 

C71.3

Malignant neoplasm of parietal lobe

 

C71.4

Malignant neoplasm of occipital lobe

 

C71.5

Malignant neoplasm of cerebral ventricle

 

C71.6

Malignant neoplasm of cerebellum

 

C71.7

Malignant neoplasm of brain stem

 

C71.8

Malignant neoplasm of overlapping sites of brain

 

C71.9

Malignant neoplasm of brain, unspecified

 

C72.0

Malignant neoplasm of spinal cord

 

C72.9

Malignant neoplasm of central nervous system, unspecified

 

C78.00

Secondary malignant neoplasm of unspecified lung

 

C78.01

Secondary malignant neoplasm of right lung

 

C78.02

Secondary malignant neoplasm of left lung

 

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

 

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

 

C79.31

Secondary malignant neoplasm of brain

 

C83.30

Diffuse large B-cell lymphoma unspecified site

 

C83.39

Diffuse large B-cell lymphoma extranodal and solid organ sites

 

C83.80

Other non-follicular lymphoma unspecified site

 

C83.89

Other non-follicular lymphoma extranodal and solid organ sites

 

C85.89

Other specified types of non-Hodgkin lymphoma, extranodal and solid organ sites

 

D32.0

Benign neoplasm of cerebral meninges

 

D32.1

Benign neoplasm of spinal meninges

 

D32.9

Benign neoplasm of meninges, unspecified

 

D42.0

Neoplasm of uncertain behavior of cerebral meninges

 

D42.1

Neoplasm of uncertain behavior of spinal meninges

 

D42.9

Neoplasm of uncertain behavior of meninges, unspecified

 

D43.0

Neoplasm of uncertain behavior of brain, supratentorial

 

D43.1

Neoplasm of uncertain behavior of brain, infratentorial

 

D43.2

Neoplasm of uncertain behavior of brain, unspecified

 

D43.4

Neoplasm of uncertain behavior of spinal cord

 

I67.89

Other cerebrovascular disease

 

Z85.038

Personal history of other malignant neoplasm of large intestine

 

Z85.068

Personal history of other malignant neoplasm of small intestine

 

Z85.118

Personal history of other malignant neoplasm of bronchus and lung

 

Z85.831

Personal history of malignant neoplasm of soft tissue

Z85.841

Personal history of malignant neoplasm of brain

Z85.848

Personal history of malignant neoplasm of other parts of nervous tissue

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA):

Jurisdiction(s): 6, K

NCD/LCD Document (s): A52370

https://www.cms.gov/medicare-coverage-database/new-search/search-results.aspx?keyword=a52370&areaId=all&docType=NCA%2CCAL%2CNCD%2CMEDCAC%2CTA%2CMCD%2C6%2C3%2C5%2C1%2CF%2CP

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC