Notification

Bevacizumab (Avastin®) and Related Biosimilars For Oncologic Use


Notification Issue Date: 02/13/2020

This version of the policy will become effective 05/15/2020.

This policy has been updated to communicate the Company's designation of two biosimilars as its preferred products: bevacizumab-awwb (Mvasi™) and bevacizumab-bvzr (Zirabev™).

Coverage for vascular diseases of the eye have been moved to Medical Policy: Intravitreal Injection of Vascular Endothelial Growth Factor (VEGF) Antagonists and Related Biosimilars 08.00.74m.

On February 20, 2020, the following language was added to the Company-Designated Preferred Products section of the Policy section: Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company.



Medical Policy Bulletin


Title:Bevacizumab (Avastin®) and Related Biosimilars For Oncologic Use

Policy #:08.00.66n

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

COMPANY-DESIGNATED PREFERRED PRODUCTS
Although there are many bevacizumab products on the market (e.g., bevacizumab [Avastin®], bevacizumab-awwb [Mvasi™], bevacizumab-bvzr [Zirabev™]), there is no reliable evidence of the superiority of any one product of bevacizumab compared to other products. The Company has designated the following bevacizumab biosimilar products as its preferred products: bevacizumab-awwb (Mvasi™) and bevacizumab-bvzr (Zirabev™).

These products are less costly and at least as likely to produce equivalent therapeutic results as the non-preferred products, which includes, but are not limited to bevacizumab (Avastin®) and any other non-preferred bevacizumab biosimilars.

According to the United States Food and Drug Administration (FDA) “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.” Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company.

NON-PREFERRED PRODUCTS
Use of non-preferred products bevacizumab (Avastin®) or any non-preferred biosimilar is considered medically necessary and, therefore, covered only for individuals who are currently receiving or have previously received a non-preferred product for the specified bevacizumab indication.

If the individual has not previously received bevacizumab (Avastin®) or a bevacizumab biosimilar to treat the specified indication, these non-preferred products are eligible for coverage when the individual has contraindication(s) or intolerance(s) to the Company designated preferred products (e.g., as documented per the FDA labeling).

BEVACIZUMAB AND RELATED BIOSIMILARS
Bevacizumab and related biosimilars are considered medically necessary and, therefore, covered for the following indications when the dosing and frequency requirements listed in Attachment A and the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NON-PREFERRED PRODUCTS Sections above are met:

AIDS-RELATED KAPOSI SARCOMA
  • Subsequent systemic therapy given with antiretroviral therapy (ART) for relapsed/refractory advanced, cutaneous, oral, visceral, or nodal disease that has progressed on or not responded to first-line systemic therapy, and progressed on alternate first-line systemic therapy

BREAST CARCINOMA, INVASIVE
In combination with paclitaxel in individuals with high tumor burden, rapidly progressing disease, and visceral crisis for recurrent or stage IV (M1) human epidermal growth factor receptor 2 (HER2)--negative disease that meets any of the following criteria:
  • Hormone receptor--negative
  • Hormone receptor--positive with visceral crisis or endocrine therapy refractory

CENTRAL NERVOUS SYSTEM TUMORS
  • Recurrent glioblastoma with progressive disease following prior therapy, as a single agent.
  • As short-course single agent therapy for management of symptoms driven by RT necrosis, poorly controlled vasogenic edema, or mass effect for any of the following conditions:
    • Adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma
    • Anaplastic glioma
    • Glioblastoma
    • Adult intracranial and spinal ependymoma (excludes subependymoma)
    • Adult medulloblastoma
    • Primary central nervous system lymphoma
    • Meningiomas
    • Brain metastases (limited or extensive)
    • Leptomeningeal metastases
    • Metastatic spine tumors
  • Treatment as a single-agent for disease progression or recurrent adult intracranial and spinal ependymoma (excludes subependymoma) if received prior RT and individuals has any of the following:
    • gross total or subtotal resection
    • localized recurrence
    • evidence of metastasis (brain, spine, or CSF)
  • Treatment of recurrent disease as a single agent (NCCN-preferred) or in combination with carmustine, lomustine, or temozolomide for anaplastic glioma or glioblastoma
  • Treatment as single agent for surgically inaccessible recurrent or progressive meningiomas when radiation is not possible.

CERVICAL CARCINOMA
  • In combination with paclitaxel and cisplatin or paclitaxel and topotecan for persistent, recurrent, or metastatic carcinoma of the cervix
  • First-line or second-line therapy as clinically appropriate (if not used previously as first-line) for local/regional recurrence or Stage IVB or distant metastases in combination with paclitaxel and cisplatin, paclitaxel and carboplatin, or paclitaxel and topotecan (NCCN-preferred regimens)

COLON OR RECTAL CARCINOMA: ADENOCARCINOMA
Colorectal
  • In individuals who have metastatic carcinoma of the colon or rectum, as first- or second-line treatment, in combination with intravenous 5-fluorouracil--based chemotherapy (e.g., IFL [irinotecan, fluorouracil, leucovorin] or FOLFOX4 [fluorouracil, leucovorin, oxaliplatin])
  • In individuals who have metastatic carcinoma of the colon or rectum, as a second-line treatment in patients who have progressed on a first-line bevacizumab (or related biosimilar) regimen, in combination with fluoropyrimidine-, irinotecan-, or fluoropyrimidine-oxaliplatin--based chemotherapy
  • For colon or rectal carcinoma as National Comprehensive Cancer Network's (NCCN) preferred anti-angiogenic therapy as primary treatment for individuals with unresectable metachronous metastases and previously received adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months:
    • In combination with irinotecan
    • In combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
  • For colon or rectal carcinoma as subsequent therapy for progression of unresectable advanced or metastatic disease:
    • In combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) regimen for disease previously treated with irinotecan-based therapy without oxaliplatin
    • In combination with FOLFOX, CapeOX, or irinotecan and oxaliplatin for individuals previously treated with fluoropyrimidine therapy without irinotecan or oxaliplatin
    • As the NCCN-preferred anti-angiogenic agent in combination with irinotecan or with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen in individuals previously treated with one of the following regimens:
      • fluoropyrimidine therapy without irinotecan or oxaliplatin
      • oxaliplatin-based therapy without irinotecan

Colon
  • For colon carcinoma, as initial treatment for unresectable synchronous liver and/or lung metastases in combination with one of the following regimens:
    • FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen
    • FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen
    • CapeOX (capecitabine and oxaliplatin) regimen
  • For colon carcinoma, in combination with capecitabine, FOLFOX, FOLFIRI, CapeOX (capecitabine and oxaliplatin), FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan), or fluorouracil/leucovorin for any of the following indications:
    • as primary treatment for locally unresectable or medically inoperable disease
    • for unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy
    • as primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with imminent or existing obstruction
    • for unresectable synchronous metastases of other sites
    • as primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy
    • for unresectable metachronous metastases that remain unresectable after primary treatment

Rectal
  • Therapy in combination with capecitabine or with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), FOLFIRI (fluorouracil, leucovorin, and irinotecan), CapeOX (capecitabine and oxaliplatin), FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan), or 5-FU/leucovorin (fluorouracil and leucovorin) regimen
    • as primary treatment for T3, N Any; T1-2, N1-2; T4, N Any; or locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant therapy
    • for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with no progression of primary tumor) after primary systemic therapy
    • following short-course radiation therapy (RT) or chemo/RT for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with progression of primary tumor) after primary systemic therapy
    • as primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for patients with existing or imminent obstruction
    • as primary treatment for synchronous unresectable metastases of other sites
    • as primary treatment for unresectable metachronous metastases in patients who have not received previous adjuvant FOLFOX or CapeOX within the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy
    • for unresectable metachronous metastases that remain unresectable after primary treatment
  • Primary treatment for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable in combination with one of the following:
    • FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
    • FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen
    • CapeOX (capecitabine and oxaliplatin) regimen
    • FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) regimen

KIDNEY CARCINOMA
  • In individuals who have metastatic renal cell carcinoma (mRCC) in combination with interferon alpha
  • In individuals with relapsed or stage IV kidney cancer with one of the following conditions:
    • clear cell histology in combination with interferon alfa-2b as first-line therapy
    • non-clear cell histology as a single agent
    • in combination with erlotinib for non-clear cell histology in selected patients with advanced papillary renal cell carcinoma including hereditary leiomyomatosis and renal cell cancer (HLRCC)
    • in combination with everolimus as systemic therapy for non-clear cell histology

MALIGNANT PLEURAL MESOTHELIOMA
In combination with pemetrexed and either cisplatin or carboplatin followed by single-agent maintenance bevacizumab as treatment of one of the following:
  • unresectable clinical stage I-IIIA disease and tumors of epithelial histology or sarcomatoid or mixed histology
  • clinical stage IIIB or IV disease or medically inoperable tumors in individuals with performance status (PS) 0-2

NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC): ADENOCARCINOMA AND LARGE CELL CARCINOMA
  • In individuals who have unresectable, locally advanced, recurrent, or metastatic NSCLC, as first-line treatment in combination with paclitaxel (Taxol®) and carboplatin (Paraplatin®)
  • Treatment for recurrent, advanced, or metastatic disease** as first-line therapy for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab or atezolizumab and performance status (PS) 0-2 in combination with atezolizumab, carboplatin and paclitaxel for nonsquamous cell histology
  • Continuation maintenance therapy as a single agent or in combination with atezolizumab for recurrent, advanced or metastatic disease** for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab or atezolizumab in individuals with PS 0-2 who achieve a response or stable disease following first-line therapy with atezolizumab/carboplatin/paclitaxel/bevacizumab for nonsquamous cell histology
  • In combination with carboplatin and either paclitaxel or pemetrexed (if contraindications to the addition of pembrolizumab or atezolizumab), or in combination with cisplatin and pemetrexed (if contraindications to the addition of pembrolizumab or atezolizumab), or in combination with atezolizumab, carboplatin and paclitaxel (if no contraindications to the addition of pembrolizumab or atezolizumab) for recurrent, advanced or metastatic disease** in individuals with PS 0 to 1, tumors of nonsquamous cell histology, and no history of recent hemoptysis for one of the following regimens:
    • initial systemic therapy for EGFR, ALK, ROS1, BRAF negative or unknown, and PD-L1 <1% or unknown
    • first-line or subsequent therapy for BRAF V600E-mutation positive tumors
    • subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, osimertinib, or dacomitinib therapy
    • subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib, or brigatinib therapy
    • subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib or ceritinib therapy
    • subsequent therapy for PD-L1 expression-positive (≥1%) tumors and EGFR, ALK negative or unknown and no prior platinum-doublet chemotherapy
  • Continuation Maintenance therapy for recurrent, advanced, or metastatic disease** in individuals with performance status 0 to 2, tumors of nonsquamous cell histology, and no history of recent hemoptysis who achieve tumor response or stable disease following initial systemic therapy, with one of the following regimens:
    • as single-agent
    • in combination with pemetrexed (if previously used with a first-line pemetrexed/platinum chemotherapy regimen)
    • in combination with atezolizumab (if previously used first-line as part of an atezolizumab/carboplatin/paclitaxel/bevacizumab regimen)

**Excludes coverage for locoregional recurrence or symptomatic local disease (with the exception of mediastinal lymph node recurrence with prior radiation therapy) with no evidence of disseminated disease.

OVARIAN CANCER (EPITHELIAL), FALLOPIAN TUBE CANCER, OR PRIMARY PERITONEAL CANCER
  • If platinum-resistant, in combination with oral cyclophosphamide, liposomal doxorubicin, weekly paclitaxel, or topotecan for persistent disease or recurrence (not including biochemical relapse) in individuals who have received no more than two prior chemotherapy regimens as NCCN-preferred therapy.
  • If platinum-resistant, as a single agent for persistent disease or recurrence (not including biochemical relapse) as NCCN-preferred therapy.
  • In combination with carboplatin and gemcitabine (if platinum-sensitive), followed by bevacizumab or related biosimilar as a single agent for persistent disease or recurrence (not including biochemical relapse) as NCCN-preferred therapy.
  • In combination with carboplatin and liposomal doxorubicin for persistent disease or recurrence (not including biochemical relapse) if platinum-sensitive, as NCCN-preferred therapy.
  • In combination with carboplatin and paclitaxel, followed by bevacizumab or related biosimilar as a single agent for one of the following:
    • In individuals who have not received prior chemotherapy and are experiencing rising CA-125 levels or clinical relapse
    • Poor surgical candidates or have low likelihood of optimal cytoreduction as:
      • neoadjuvant therapy
      • continued treatment for stable disease following neoadjuvant therapy
    • Primary treatment for individuals with incomplete previous surgery and/or staging with Stage II-IV and suspected unresectable residual disease
    • Primary adjuvant therapy for pathologic Stage II-IV disease with endometroid or serous histology
    • Adjuvant treatment for pathologic stage I-IV disease and carcinosarcoma histology, as NCCN-preferred therapy.
    • Adjuvant treatment for pathologic stage II-IV disease and clear cell histology.
    • Adjuvant treatment for pathologic stage II-IV disease and mucinous histology.
    • Adjuvant treatment for pathologic stage II-IV, grade 1 endometrioid carcinoma.
    • Adjuvant treatment for pathologic stage II-IV low-grade serous carcinoma or borderline epithelial tumors with invasive implants.
    • Persistent disease or recurrence, platinum-sensitive disease (not including biochemical relapse) as NCCN-preferred therapy
  • Maintenance therapy as a single agent if used previously as part of a combination therapy:
    • Partial or complete remission or stable disease following primary therapy for Stage II-IV disease
    • Partial or complete response following recurrence therapy with bevacizumab for platinum-sensitive disease
  • In individuals who have malignant sex cord-stromal tumors (stage II-IV) as therapy for clinical relapse, as a single agent

SOFT TISSUE SARCOMA
  • In individuals with angiosarcoma as a single agent
  • In individuals with solitary fibrous tumor or hemangiopericytoma in combination with temozolomide

UTERINE CANCER/ ENDOMETRIAL CANCER
  • As a single agent for disease that has progressed on prior cytotoxic chemotherapy
  • In combination with carboplatin and paclitaxel for advanced and recurrent disease

VULVAR CANCER
In combination with cisplatin and paclitaxel (NCCN-preferred regimen):
  • as additional treatment for unresectable locally advanced disease clinically positive for residual tumor at the primary site and/or nodes
  • as additional treatment for locally advanced disease with positive margins following resection
  • as primary treatment for metastatic disease beyond the pelvis
  • for isolated groin/pelvic recurrence if prior external beam radiation therapy (EBRT)
  • for clinical nodal or distant recurrence with multiple pelvic nodes, distant metastasis, or prior pelvic EBRT

NOT MEDICALLY NECESSARY

For individuals receiving their first course of bevacizumab, use of the non-preferred reference product bevacizumab (Avastin®) or any non-preferred biosimilar, is considered not medically necessary and, therefore, not covered since they are more costly than the preferred products that are at least as likely to produce equivalent therapeutic results for that individual's illness.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of bevacizumab and related biosimilars are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

Refer to Attachment A for dosing and frequency requirements for bevacizumab and related biosimilars.

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of bevacizumab and related biosimilars. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of bevacizumab and related biosimilars outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for bevacizumab and related biosimilars.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of bevacizumab and related biosimilars is requested outside of the Dosing and Frequency Guidelines listed in this Policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.
Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The ECOG has developed the ECOG Performance Status; it was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states, "These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."
ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, bevacizumab and related biosimilars are covered under the medical benefits of the Company’s products when the medical necessity criteria, dosing and frequency requirements, and the precertification/preapproval requirements listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The initial approval for the use of bevacizumab was granted by the FDA on February 26, 2004. Supplemental approvals have since been issued. The safety, effectiveness and pharmacokinetic profile of bevacizumab in the pediatric population have not been established.

The FDA has issued subsequent approvals for biosimilar products.

Description

Bevacizumab and related biosimilars are recombinant humanized monoclonal IgG1 antibodies that work by binding to and inhibiting the action of vascular endothelial growth factor (VEGF). VEGF is a substance that binds to certain cells to stimulate new blood vessel formation (angiogenesis). When VEGF is bound to bevacizumab and related biosimilars, it cannot stimulate the formation and growth of new blood vessels. Bevacizumab and related biosimilars are thought to enhance the effects of chemotherapy.

The US Food and Drug Administration (FDA) has granted approval for the use of bevacizumab and related biosimilars for the following indications:
  • In individuals who have metastatic carcinoma of the colon or rectum, as first- or second-line treatment, in combination with intravenous 5-fluorouracil--based chemotherapy
  • In individuals who have metastatic carcinoma of the colon or rectum, as a second-line treatment in patients who have progressed on a first-line bevacizumab regimen, in combination with fluoropyrimidine-, irinotecan-, or fluoropyrimidine-oxaliplatin--based chemotherapy
  • In individuals who have unresectable, locally advanced, recurrent, or metastatic non-squamous non-small cell lung cancer, as first-line treatment in combination with paclitaxel (Taxol®) and carboplatin (Paraplatin®)
  • In individuals who have recurrent glioblastoma, as a single agent
  • In individuals who have metastatic renal cell carcinoma, in combination with interferon alfa
  • In individuals who have persistent, recurrent, or metastatic carcinoma of the cervix, in combination with paclitaxel and cisplatin or paclitaxel and topotecan
  • In individuals who have stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection, in combination with carboplatin and paclitaxel, followed by bevacizumab as a single agent.
  • In individuals who have platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan.
  • In individuals who have platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer when given either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine, followed by bevacizumab as a single agent.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

In 2008, the FDA gave accelerated approval for the treatment of metastatic breast cancer. However in 2011, the FDA withdrew this indication, since further studies showed only a small delay in tumor growth compared to earlier trials, no increase in overall survival, and an increase in the incidence of serious adverse events. Considering all information from these studies, the FDA concluded that the risks of this drug outweighed its benefits in the treatment of patients with metastatic breast cancer. Although this indication was withdrawn from the FDA, drug compendia still support the use of bevacizumab for the treatment of metastatic breast cancer.
References

American Hospital Formulary Service (AHFS). Bevacizumab (Avastin®). Drug Information 2019. [Lexicomp Online Web site]. 09/22/16. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed May 1, 2019.


Bevacizumab (Avastin®) labeling. Genentech, Inc., South San Francisco, CA. 02/2019. Available at: https://www.avastin-hcp.com/ . Accessed April 23, 2019.

Eastern Cooperative Oncology Group (ECOG). ECOG performance status. 2019. Available at: http://ecog-acrin.org/resources/ecog-performance-status . Accessed May 1, 2019.

Elsevier’s Clinical Pharmacology Compendium. bevacizumab (Avastin). 12/11/18. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/monograph/2709?n=Avastin [via subscription only]. Accessed May 1, 2019.

Lexi-Drugs Compendium. bevacizumab (Avastin). 04/16/19. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed May 1, 2019.

National Cancer Institute (NCI). Ovarian epithelial cancer treatment (PDQ®). Health professional version. [NCI Web site]. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/HealthProfessional/page1 . Accessed May 1, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Breast cancer. v.1.2019. [NCCN Web site]. 03/14/2019. Available at: http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed April 23, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Central nervous system cancers. v.1.2019. [NCCN Web site]. 03/05/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cns_blocks.pdf. Accessed April 30, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Cervical cancer. v.4.2019. [NCCN Web site]. 03/29/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cervical_blocks.pdf . Accessed April 26, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Colon cancer. v.1.2019. [NCCN Web site]. 03/15/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf . Accessed April 29, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Kidney cancer. v.4.2019. [NCCN Web site]. 04/25/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney_blocks.pdf . Accessed April 26, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Non-small cell lung cancer. v.4.2019. [NCCN Web site]. 04/29/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf. Accessed April 30, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Ovarian cancer, including fallopian tube cancer and primary peritoneal cancer. v.1.2019. [NCCN Web site]. 03/08/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ovarian_blocks.pdf . Accessed April 26, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Rectal cancer. v.1.2019. [NCCN Web site]. 04/25/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal_blocks.pdf . Accessed April 30, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Soft Tissue Sarcoma. v.2.2019. [NCCN Web site]. 02/07/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/sarcoma_blocks.pdf . Accessed April 26, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. Uterine Neoplasms. v.3.2019. [NCCN Web site]. 02/27/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine_blocks.pdf . Accessed April 30, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™.Bevacizumab (Avastin®). 2019. [NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed April 23, 2019.

Pope WB, Lai A, Nghiemphu P, et al. MRI in patients with high-grade gliomas treated with bevacizumab and chemotherapy. Neurology. 2006;66(8):1258-1260.

Salah Uddin ABM, Jarmi T. Neurologic Manifestations of Glioblastoma multiforme. [eMedicine Web site]. 11/09/15. Available at: http://emedicine.medscape.com/article/1156220-overview . Accessed May 1, 2019.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Bevacizumab (Avastin®). 04/12/19. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ [via subscription only]. Accessed May 1, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Avastin (bevacizumab). Package insert. [FDA Web site]. 04/03/2019. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed April 23, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Mvasi™(bevacizumab-awwb). Package insert. [FDA Web site]. 09/14/17. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761028 . Accessed April 26, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. bevacizumab-bvzr (Zirabev™). Package insert. [FDA Web site]. 06/27/2019. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed September 18, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Postmarket drug safety information for patients and providers. Questions and answers about avastin. 12/16/2010. Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm237095.htm . Accessed April 26, 2019.

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13(4):1253-1259.




Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

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 colon

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

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 and 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

C45.0 Mesothelioma of pleura

C48.0 Malignant neoplasm of retroperitoneum

C48.1 Malignant neoplasm of specified parts of peritoneum

C46.0 Kaposi's sarcoma of skin

C46.1 Kaposi's sarcoma of soft tissue

C46.2 Kaposi's sarcoma of palate

C46.3 Kaposi's sarcoma of lymph nodes

C46.4 Kaposi's sarcoma of gastrointestinal sites

C46.50 Kaposi's sarcoma of unspecified lung

C46.51 Kaposi's sarcoma of right lung

C46.52 Kaposi's sarcoma of left lung

C46.7 Kaposi's sarcoma of other sites

C46.9 Kaposi's sarcoma, unspecified

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

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

C57.8 Malignant neoplasm of overlapping sites of female genital organs

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

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




HCPCS Level II Code Number(s)


C9257 Injection, bevacizumab, 0.25 mg

J9035 Injection, bevacizumab, 10 mg

Q5107 Injection, bevacizumab-awwb, biosimilar, (mvasi), 10 mg

Q5118 Injection, bevacizumab-bvzr, biosimilar, (Zirabev), 10 mg




Revenue Code Number(s)

N/A

Coding and Billing Requirements

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).
Cross References

Attachment A: Bevacizumab (Avastin®) and Related Biosimilars For Oncologic Use
Description: Dosing and Frequency Requirements




Policy History

Revisions from 08.00.66n:
05/15/2020This policy has been updated to communicate the Company's designation of two biosimilars as its preferred products: bevacizumab-awwb (Mvasi™) and bevacizumab-bvzr (Zirabev™).

Coverage for vascular diseases of the eye have been moved to Medical Policy: Intravitreal Injection of Vascular Endothelial Growth Factor (VEGF) Antagonists and Related Biosimilars 08.00.74m.

On February 20, 2020, the following language was added to the Company-Designated Preferred Products section of the Policy section: Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company.


Revisions from 08.00.66m:
10/01/2019This policy has been identified for the HCPCS code update, effective 10/01/2019.

The following HCPCS code has been added to this policy:
Q5118 Injection, bevacizumab-bvzr, biosimilar, (Zirabev), 10 mg

Revisions from 08.00.66l:
06/17/2019This policy has undergone a routine review and the medical necessity criteria, including dosing and frequency requirements, have been revised to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

Revisions from 08.00.66k:
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS code has been added to this policy:
Q5107 Injection, bevacizumab-awwb, biosimilar, (mvasi), 10 mg

The following HCPCS code has been removed from this policy:
J3590 Unclassified biologics


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 05/15/2020
Version Issued Date: 05/15/2020
Version Reissued Date: N/A

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