​

Last Review Date: 06/04/2024

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, 09/2021, 12/2021, 03/2022, 05/2022, 09/2022, 11/2022, 03/2023, 06/2023, 09/2023, 12/2023, 01/2024, 03/2024, 06/2024

1. Length of Authorization ⁹

Coverage will be provided for 6 months and may be renewed (unless otherwise specified).

• Adult CNS Cancers (symptom management): Coverage will be provided for twelve (12) weeks and may NOT be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:
   Avastin, Mvasi, Zirabev, Alymsys, Vegzelma, Avzivi:

• 100 mg/4 mL single-dose vial: 3 vials 21 days
• 400 mg/16 mL single-dose vial: 4 vials per 21 days

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

Oncology indications (J9035/Q5107/Q5118/Q5126/Q5129):

• CRC & Appendiceal Adenocarcinoma, CNS Cancers, RCC:
  • 120 billable units per 14 days
• Small Bowel Adenocarcinoma & Ampullary Adenocarcinoma:
  • 90 billable units per 14 days
• NSCLC, Cervical Cancer, HCC, Vaginal Cancer, Vulvar Cancer, & Mesotheliomas:
  • 170 billable units per 21 days
• All other indications:
  • 170 billable units per 14 days

3. Initial Approval Criteria ^1-6

Coverage is provided in the following conditions:

• Patient is at least 18 years of age, unless otherwise specified; AND

Universal Criteria 1-6

• Patient has no recent history of hemoptysis (i.e., the presence of ≥2.5 mL of blood in sputum); 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

Ampullary Adenocarcinoma ‡ 7

• Used in combination with a fluoropyrimidine- (e.g., 5-fluorouracil/5-FU or capecitabine) based regimen for intestinal type disease; AND
  • Used as first-line therapy for unresectable localized or metastatic disease; OR
  • Used for disease progression

Adult Central Nervous System (CNS) Cancers † ‡ Ф 1-7,9,28,29

• Used as single-agent short-course therapy for symptom management related to radiation necrosis, poorly controlled vasogenic edema, or mass effect; AND
  • Patient has a diagnosis of one of the following CNS cancers ‡:
  • Circumscribed Glioma
  • Primary CNS Lymphoma
  • Meningiomas
  • Brain or Spine metastasesMedulloblastoma
  • Glioblastoma/Gliosarcoma/H3-mutated high-grade glioma
  • IDH-mutant Astrocytoma (WHO Grade 2-4)
  • IDH-mutant, 1p19q codeleted Oligodendroglioma (WHO Grade 2 or 3)
  • Intracranial or Spinal Ependymoma (excluding subependymoma); OR
• Used for recurrent or progressive disease; AND
  • Patient has a diagnosis of one of the following CNS cancers:
    • IDH-mutant, 1p19q codeleted Oligodendroglioma (WHO Grade 3) ‡
    • Glioblastoma/Gliosarcoma/H3-mutated high-grade glioma † ‡
    • IDH-mutant Astrocytoma (WHO Grade 3 or 4) ‡; AND
  • Used as a single agent; OR
  • Used in combination with carmustine, lomustine, or temozolomide; AND
    • Patient has failed bevacizumab monotherapy; OR
• Used as a single agent for Intracranial or Spinal Ependymoma (excluding subependymoma) after prior radiation therapy ‡; OR
• Used as a single agent for surgically inaccessible Meningiomas when radiation is not possible ‡

Cervical Cancer † ‡ 1-7,31,50,61

• Patient has persistent, recurrent, or metastatic disease; AND
  • Disease has adenocarcinoma, adenosquamous, or squamous cell carcinoma histology; AND
    • Used in combination with paclitaxel AND either cisplatin, carboplatin, or topotecan^; OR
    • Used in combination with pembrolizumab, paclitaxel, AND cisplatin or carboplatin^; AND
      • Tumor expresses PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved or CLIA compliant testv; OR
    • Used as a single agent as subsequent therapy; OR
  • Patient has small cell neuroendocrine carcinoma of the cervix (NECC); AND
    • Used in combination with paclitaxel and topotecan^; AND
      • Used as first-line therapy; OR
      • Used as subsequent therapy (if not previously used as first-line); OR
    • Used as a single agent as subsequent therapy

^ Bevacizumab may be continued as a maintenance therapy

Colorectal Cancer (CRC) † ‡ 1-7,20-25,51

• Will not be used as part of adjuvant treatment; AND
  • Used in combination with intravenous fluorouracil-based chemotherapy as first- or second-line treatment for metastatic disease †; OR
  • Used in combination with a fluoropyrimidine- (e.g., 5-fluorouracil/5-FU or capecitabine) based regimen as first-line or subsequent therapy for metastatic, unresectable (or medically inoperable), or advanced disease; AND
    • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
      • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy; OR
  • Used in combination with irinotecan as initial treatment for unresectable metastatic disease; 
    • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; AND
    • Patient received previous FOLFOX or CapeOX within the past 12 months; OR
  • Used in combination irinotecan as subsequent therapy for advanced or metastatic disease; AND
    • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
      • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy; OR
  • Used in combination with a fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based regimen (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; AND
    • Patient progressed through all available regimens (e.g., oxaliplatin-based therapy, irinotecan-based therapy, fluoropyrimidine-based therapy, etc.)*; AND
      • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
        • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy; OR
  • Used as primary treatment for T3, N Any; T1-2, N1-2; T4, N Any rectal cancer; AND
    • Used in combination with a fluoropyrimidine- (e.g., 5-fluorouracil/5-FU or capecitabine) based regimen; AND
      • Used if resection is contraindicated following total neoadjuvant therapy; AND
        • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
        • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
          • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy; OR
        • Used if resection is contraindicated following neoadjuvant/definitive immunotherapy; AND
          • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease 

*Refer to NCCN Colon and Rectal Cancer guidelines for regimens.

Appendiceal Adenocarcinoma – Colon Cancer ‡ 7,48

• Used as adjuvant therapy; AND
  • Used in combination with pemetrexed AND either cisplatin or carboplatin (if cisplatin ineligible); AND
  • Patient has unicavitary disease with epithelioid histology; AND
  • Patient has surgical/pathologic high-risk features** and no neoadjuvant therapy was given; OR
• Used as first-line therapy; AND
  • Used in combination with pemetrexed AND either cisplatin or carboplatin (if cisplatin ineligible); AND
    • Patient has biphasic/sarcomatoid histology or bicavitary disease; OR
    • Patient has unicavitary disease with epithelioid histology; AND
      • Patient is medically inoperable and/or complete cytoreduction is not achievable (including high-risk features**); OR
      • Patient has recurrent disease after prior cytoreductive surgery (CRS) + hyperthermic intraperitoneal (IP) chemotherapy (HIPEC) and no previous adjuvant systemic therapy was given; OR
• Used as subsequent therapy; AND
  • Used in combination with pemetrexed AND either cisplatin or carboplatin (if cisplatin ineligible); AND
    • Immunotherapy was administered as first-line treatment; OR
    • Used as a rechallenge if pemetrexed-based treatment was administered first-line with good response; OR
  • Used in combination with atezolizumab; AND
    • Patient has not received previous therapy with immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab, durvalumab, avelumab, cemiplimab, dostarlimab, nivolumab/relatlimab, retifanlimab, toripalimab, etc.)

*Note: May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.

** High-risk features include Ki-67 >9%, nodal metastasis, high tumor burden (Peritoneal Cancer Index [PCI] >17), completeness of cytoreduction (CC) score >1, biphasic disease, or bicavitary disease.

Pleural* Mesothelioma (PM) ‡ 7,40,52

• Used as first-line therapy; AND
  • Used in combination with pemetrexed AND either cisplatin or carboplatin (if cisplatin ineligible); AND
    • Patient has clinical stage I–IIIA disease with epithelioid histology; OR
    • Patient has clinical stage IIIB or IV disease, sarcomatoid or biphasic histology, or medically inoperable disease; OR
• Used as subsequent therapy; AND
  • Used in combination with pemetrexed AND either cisplatin or carboplatin (if cisplatin ineligible); AND
    • Immunotherapy was administered as first-line treatment; OR
    • Used as a rechallenge if pemetrexed-based treatment was administered first-line with good response

*Note: May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.

Non-Squamous Non-Small Cell Lung Cancer (NSCLC) † ‡ 1-7,13,15,16,26,27

• 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 in combination with erlotinib for EGFR exon 19 deletion or exon 21 L858R mutations; OR
    • Used in combination with carboplatin and paclitaxel †; OR
    • Used for one of the following:
      • Patients with a performance status (PS) 0-1 who have tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive) and PD-L1 expression < 1%
      • PD-L1 expression positive (PD-L1 ≥ 1%) tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
      • Patients with a PS 0-1 who are positive for one of the following molecular biomarkers: EGFR exon 20, BRAF V600E, NTRK1/2/3 gene fusion, MET exon 14 skipping, RET rearrangement, or ERBB2 (HER2); AND
    • Used in combination with one of the following:
      • Pemetrexed AND either carboplatin or cisplatin in patients with contraindications¥ to PD-1 or PD-L1 inhibitors
      • Atezolizumab, carboplatin, and paclitaxel; OR
  • Used as subsequent therapy in patients with a PS 0-1; AND
    • Used for one of the following:
      • EGFR exon 19 deletion or exon 21 L858R mutation, EGFR S768I, L861Q, and/or G719X mutation, ALK rearrangement, or ROS1 rearrangement positive tumors AND patient received prior targeted therapy§ for those aberrations
      • BRAF V600E mutation, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, or RET rearrangement positive tumors
      • PD-L1 expression positive (PD-L1 ≥ 1%) tumors that are negative for actionable molecular biomarkers* after prior PD-1/PD-L1 inhibitor therapy but no prior platinum-containing chemotherapy; AND
    • Used in combination with one of the following:
      • Carboplatin and paclitaxel in patients with contraindications¥ to PD-1 or PD-L1 inhibitors
      • Pemetrexed AND either carboplatin or cisplatin in patients with contraindications¥ to PD-1 or PD-L1 inhibitors
      • Atezolizumab, carboplatin, and paclitaxel (excluding use in patients who have received prior PD-1/PD-L1 inhibitor therapy); OR
  • Used as continuation maintenance therapy in patients who achieved a tumor response or stable disease after first-line systemic therapy; AND
    • Used as a single agent (bevacizumab must have been included in the first-line regimen); 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 as continuation of therapy following disease progression on erlotinib with bevacizumab; AND
    • Patient has asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited progression; AND
    • Patient has T790M negative disease

Ovarian, Fallopian Tube, and Primary Peritoneal Cancer † ‡ Ф 1-7,14,32-35,53

• Patient has malignant stage II-IV sex cord-stromal tumors ‡; AND
  • Used as a single agent for clinically relapsed disease; OR
• Patient has epithelial* ovarian, fallopian tube, or primary peritoneal cancer †; AND
  • Patient has persistent or recurrent disease; 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 with carboplatin AND either gemcitabine, paclitaxel † or 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, gemcitabine, liposomal doxorubicin, paclitaxel, or topotecan; OR
        • Used in combination with oral cyclophosphamide and pembrolizumab; OR
        • Used in combination with mirvetuximab soravtansine-gynx (in folate receptor-alpha expressing tumors); OR
        • Used in combination with carboplatin AND either gemcitabine, paclitaxel or liposomal doxorubicin; OR
        • Used in combination with paclitaxel and carboplatin for rising CA-125 levels or clinical relapse in patients who have received no prior chemotherapy (mucinous, clear cell, carcinosarcoma, endometrioid, and high-grade serous histology only); OR
  • Used in combination with paclitaxel and carboplatin for recurrence in patients who have received no prior chemotherapy (low-grade serous histology only); OR
  • Used as maintenance therapy; AND
    • Used for stage II-IV disease 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, HR deficient, or status unknown (grade 2/3 endometrioid and high-grade serous histology only); OR
      • Used in combination with olaparib or niraparib (if unable to tolerate olaparib); AND
        • Patient is BRCA1/2 wild-type or unknown AND HR deficient (grade 2/3 endometrioid and high-grade serous histology only); OR
        • Patient has a germline or somatic BRCA1/2 mutation (grade 2/3 endometrioid, high-grade serous, clear cell, carcinosarcoma histology only); OR
      • Used as a single agent following recurrence therapy with chemotherapy plus bevacizumab for platinum-sensitive disease; OR
      • Used as continued treatment for stable disease following neoadjuvant therapy (endometrioid and serous histology only); AND
        • Used in combination with carboplatin AND paclitaxel or docetaxel; OR
        • Used in combination with oxaliplatin and docetaxel; OR
  • Used as neoadjuvant therapy (endometrioid and serous histology only); AND
    • Used in combination with one of the following:
      • Carboplatin AND paclitaxel or docetaxel
      • Oxaliplatin and docetaxel; AND
    • Patient is a poor surgical candidate or has a low likelihood of optimal cytoreduction; OR
  • Used as adjuvant therapy; AND
    • Used in combination with oxaliplatin and docetaxel; AND
      • Patient has pathologic stage II-IV disease (mucinous, clear cell, carcinosarcoma, grade 2/3 endometrioid, and high-grade serous histology only); OR
      • Used following interval debulking surgery (IDS) in patients with a response or stable disease to neoadjuvant therapy (endometrioid and serous histology only); AND
        • Patient is a poor surgical candidate or has a low likelihood of optimal cytoreduction; OR
      • Used in combination with carboplatin AND paclitaxel or docetaxel; AND
        • Patient has pathologic stage II-IV disease; OR
        • Used following interval debulking surgery (IDS) in patients with a response or stable disease to neoadjuvant therapy (endometrioid and serous histology only); AND
          • Patient is a poor surgical candidate or has a low likelihood of optimal cytoreduction

*Epithelial subtypes include serous, endometrioid, carcinosarcoma (malignant mixed Müllerian tumors [MMMTs] of the ovary), clear cell, mucinous, and borderline epithelial tumors (also known as low malignant potential [LMP] tumors).

Pediatric Central Nervous System (CNS) Cancers ‡ 7,47,56-60

• Patient is ≤ 18 years of age; AND
• Patient has recurrent or progressive disease; AND
  • Patient has diffuse high-grade glioma (excluding oligodendroglioma, IDH-mutant and 1p/19q co-deleted or astrocytoma IDH-mutant); AND
    • Used as a single agent for palliation; OR
  • Patient has medulloblastoma; AND
    • Used as part of the TEMR regimen (temozolomide, irinotecan, bevacizumab); OR
    • Used as part of MEMMAT regimen (thalomide, celecoximb, fenofibrate, etoposide, cyclophosphamide, bevacizumab)

Renal Cell Carcinoma (RCC) † ‡ Ф 1-7,30

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

Small Bowel Adenocarcinoma ‡ 7,19

• Patient has advanced or metastatic disease; AND
• Used in combination with a fluoropyrimidine- (e.g., 5-fluorouracil/5-FU or capecitabine) based regimen

Soft Tissue Sarcoma ‡ 7,37,42

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

Vaginal Cancer ‡ 7,31,61

• Patient has recurrent or metastatic disease; AND
  • Used in combination with paclitaxel AND either cisplatin, carboplatin, or topotecan; AND
    • Used as first-line therapy; OR
    • Used as subsequent therapy (if not previously used as first-line); OR
  • Used in combination with pembrolizumab, paclitaxel, AND either cisplatin or carboplatin; AND
    • Tumor expresses PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved or CLIA compliant testv; AND
      • Used as first-line therapy; OR
      • Used as subsequent therapy (if not previously used as first-line); OR
  • Used as a single agent; AND
    • Used as subsequent therapy

Vulvar Cancer ‡ 7,31

• Used in combination with paclitaxel and cisplatin; AND
• Patient has advanced, recurrent, or metastatic disease; AND
  • Used as first-line therapy; OR
  • Used as subsequent therapy (if not previously used)

v If confirmed using an FDA-approved assay – http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-7,9

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the 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, necrotizing fasciitis, hemorrhage, arterial and venous thromboembolic events (ATE & VTE), uncontrolled hypertension, posterior reversible encephalopathy syndrome (PRES), nephrotic syndrome, proteinuria, severe infusion-related reactions, ovarian failure, congestive heart failure (CHF), etc.; AND
   

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

• Coverage may NOT be renewed

Adult CNS Cancers (in combination with carmustine, lomustine, or temozolomide):

• Refer to Section III for criteria

Cervical Cancer (maintenance therapy):

• Refer to Section III for criteria

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

• Refer to Section III for criteria

Endometrial Carcinoma (Uterine Neoplasms) (maintenance therapy)

• Refer to Section III for criteria

PeM* (combination therapy with atezolizumab):

• Refer to Section III for criteria

* Includes use for pericardial mesothelioma and tunica vaginalis testis mesothelioma.

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

• Refer to Section III for criteria

Ovarian Fallopian Tube, and Primary Peritoneal Cancer (maintenance therapy):

• Refer to Section III for criteria

5. Dosage/Administration ^{1-6,8,9,14,19,31,37,38,40-49,54}

6. Billing Code/Availability Information

HCPCS Code(s):

• 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
• Q5126 – Injection, bevacizumab-maly, biosimilar, (alymsys), 10 mg; 1 billable unit = 10 mg
• Q5129 – Injection, bevacizumab-adcd, biosimilar, (vegzelma), 10 mg; 1 billable unit = 10 mg
• J9999 – Not otherwise classified, antineoplastic drugs (Avzivi only)

    NDC(s):

• Avastin single-dose vial, 100 mg/4 mL solution for injection: 50242-0060-xx
• Avastin single-dose vial, 400 mg/16 mL solution for injection: 50242-0061-xx
• Mvasi single-dose vial, 100 mg/4 mL solution for injection: 55513-0206-xx
• Mvasi single-dose vial, 400 mg/16 mL solution for injection: 55513-0207-xx
• Zirabev single-dose vial, 100 mg/4 mL solution for injection: 00069-0315-xx
• Zirabev single-dose vial, 400 mg/16 mL solution for injection: 00069-0342-xx
• Alymsys single-dose vial, 100 mg/4 mL solution for injection: 70121-1754-xx
• Alymsys single-dose vial, 400 mg/16 mL solution for injection: 70121-1755-xx
• Vegzelma single-dose vial, 100 mg/4 mL solution for injection: 72606-0011-xx
• Vegzelma single-dose vial, 400 mg/16 mL solution for injection: 72606-0012-xx
• Avzivi single-dose vial, 100 mg/4 mL solution for injection: 82143-0001-xx
• Avzivi single-dose vial, 400 mg/16 mL solution for injection: 82143-0002-xx

7. References

1. Avastin [package insert]. South San Francisco, CA; Genentech, Inc.; September 2022. Accessed May 2024.
2. Mvasi [package insert]. Thousand Oaks, CA; Amgen, Inc.; February 2023. Accessed May 2024.
3. Zirabev [package insert]. New York, NY; Pfizer, Inc.; February 2023. Accessed May 2024.
4. Alymsys [package insert]. Bridgewater, NJ; Amneal Pharmaceuticals LLC; April 2022. Accessed May 2024.
5. Vegzelma [package insert]. Incheon, Republic of Korea; Celltrion, Inc.; February 2023. Accessed May 2024.
6. Avzivi [package insert]. Guangzhou, Guangdong Province, China; Bio-Thera Solutions, Ltd.; December 2023. Accessed May 2024.
7. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) bevacizumab. National Comprehensive Cancer Network, 2024. 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 2024.
8. 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
9. 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.
10. 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.
11. 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
12. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
13. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer 5.2024. National Comprehensive Cancer Network, 2024. 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 2024.
14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer 1.2024. National Comprehensive Cancer Network, 2024. 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 2024.
15. 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.
16. 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.
17. 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.
18. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatocellular Carcinoma 1.2024. National Comprehensive Cancer Network, 2024. 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 2024.
19. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Small Bowel Adenocarcinoma 3.2024. National Comprehensive Cancer Network, 2024. 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 2024.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. Wick W, Gorlia T, Bendszus M, et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med 2017; 377:1954-1963.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76.
40. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Mesothelioma: Pleural 1.2024. National Comprehensive Cancer Network, 2024. 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 2024.
41. 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.
42. 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.
43. 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.
44. 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.
45. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Mesothelioma: Peritoneal 1.2024. National Comprehensive Cancer Network, 2024. 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 2024.
46. Raghav KPS, Overman MJ, Liu S, et al. A phase II trial of atezolizumab and bevacizumab in patients with relapsed/refractory and unresectable malignant peritoneal mesothelioma. J Clin Oncol 2020;38:9013-9013.
47. Grill J, Massimino M, Bouffet E, et al. Phase II, Open-Label, Randomized, Multicenter Trial (HERBY) of Bevacizumab in Pediatric Patients With Newly Diagnosed High-Grade Glioma. J Clin Oncol 2018 Apr 1;36(10):951-958. Doi: 10.1200/JCO.2017.76.0611. Epub 2018 Feb 7.
48. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer Version 2.2024. National Comprehensive Cancer Network, 2024. 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 2024.
49. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer Version 2.2024. National Comprehensive Cancer Network, 2024. 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 2024.
50. Frumovitz M, Munsell MF, Burzawa JK, et al. Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in recurrent small cell neuroendocrine carcinoma of the cervix. Gynecol Oncol. 2017 Jan;144(1):46-50. Doi: 10.1016/j.ygyno.2016.10.040. Epub 2016 Nov 4. PMID: 27823771; PMCID: PMC5873577.
51. Prager GW, Taieb J, Fakih M, et al.; SUNLIGHT Investigators. Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med. 2023 May 4;388(18):1657-1667. Doi: 10.1056/NEJMoa2214963. PMID: 37133585.
52. Bearz A, Talamini R, Rossoni G, et al. Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience. BMC Res Notes 2012;5:482
53. Nagao S, Kogiku A, Suzuki K, et al. A phase II study of the combination chemotherapy of bevacizumab and gemcitabine in women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Ovarian Res 2020;13:14
54. Gulhati P, Raghav K, Shroff RT, et al. Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study. Cancer 2017;123:1011-1017
55. Qin S, Chen M, Cheng AL, Kaseb AO, et al. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Nov 18;402(10415):1835-1847. doi: 10.1016/S0140-6736(23)01796-8.
56. Grill J, Massimino M, Bouffet E, et al. Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed highgrade glioma. J Clin Oncol 2018;36:951-958.
57. Peyrl A, Chocholous M, Kieran MW, et al. Antiangiogenic metronomic therapy for children with recurrent embryonal brain tumors. Pediatr Blood Cancer 2012;59:511- 517.
58. Slavc I, Mayr L, Stepien N, et al. Improved long-term survival of patients with recurrent medulloblastoma treated with a "MEMMAT-like" metronomic antiangiogenic approach. Cancers (Basel) 2022;14:5128.
59. Winnicki C, Leblond P, Bourdeaut F, et al. Retrospective national "Real Life" experience of the SFCE with the metronomic MEMMAT and MEMMAT-like protocol. J Clin Med 2023;12:1415.
60. Levy AS, Krailo M, Chi S, et al. Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma of childhood: Report of a COG randomized Phase II screening trial. Pediatr Blood Cancer 2021;68:e29031
61. Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 2021;385:1856-1867.
62. National Government Services, Inc. Local Coverage Article: Billing and Coding: Bevacizumab and biosimilars (A52370). Centers for Medicare & Medicaid Services, Inc. Updated on 06/21/2023 with effective date 07/01/2023. Accessed April 2024.

Appendix 1 – Covered Diagnosis Codes

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

The preceding information is intended for non-Medicare coverage determinations. 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 Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

​