CurrentAnthemPolicy CC-0107

Medical Drug Clinical Criteria - Bevacizumab for Non-ophthalmologic Indications

Clinical coverage criteria for Avastin (bevacizumab) and listed biosimilars (Alymsys, Avzivi, Jobevne, Mvasi, Vegzelma, Zirabev) for non-ophthalmologic oncologic and related indications, including FDA-approved and NCCN-recommended uses, exclusions, biosimilar extrapolation, and step therapy guidance. This is Part 1 of 2 of the policy.

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria - Bevacizumab for Non-ophthalmologic Indications

Policy CodePolicy CC-0107

Change TypeStep therapy and coding updates (03/01/2026; historical updates)

Effective DateMar 1, 2026

Next Review Date

Key ActionRequests must meet the listed indication-specific clinical criteria and required documentation (prior therapies, biomarkers, ECOG/Child-Pugh status) for prior authorization.

SourceLink

POLICY UPDATE CHANGES

Step therapy table updates performed on 03/01/2026 and multiple prior dates.

Coding update on 11/21/2025: Removed Jobevne from HCPCS NOC C9399 and J9999 effective 12/31/25 and added Q5160 for Jobevne effective 1/1/26.

05/16/2025: Jobevne (bevacizumab-nwgd) added to criteria and step therapy following FDA approval.

Multiple historical updates clarified indications (NCCN-based) such as CNS cancers, NF2 vestibular schwannomas, colorectal mutation-specific uses, ovarian cancer subtypes, combination uses (e.g., with atezolizumab), and mesothelioma indications.

MultipleCovered Indications Listed

Several

Related Billing Codes

J2270-INJECTION-MORPHINE-SULFATE-UP-TO-10

CPT J2270: Injection of Morphine Sulfate, Up to 10 mg

J3490-UNCLASSIFIED

CPT J3490: Unclassified Drug Administration in Outpatient Hospital Settings

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Biosimilars included

ManyICD-10 codes listed (partial)

7Distinct HCPCS/Q/J code groups listed

multi-yearDocument history range

Coverage summary

This policy (Part 1 of 2) addresses clinical coverage for Avastin (bevacizumab) and listed biosimilars (Alymsys, Avzivi, Jobevne, Mvasi, Vegzelma, Zirabev) for non-ophthalmologic oncologic and related indications. Coverage is covered with criteria and governed by indication-specific approval rules, step therapy and prior authorization processes. The document header and history show the policy was last revised with an effective date of 2026-03-01 and last reviewed 05/16/2025. Payer/program-level preferred vs non-preferred agent lists and coding guidance (HCPCS/J/Q codes) are included in the policy metadata and step therapy tables.

Quick facts & thresholds

ECOG requirementECOG performance status 0-2 required for multiple indications

Child-Pugh for HCCChild-Pugh class A or B required for hepatocellular carcinoma

TMB ultra-hypermutated exampleUltra-hypermutated phenotype example: TMB >50 mut/Mb

HCPCS / J / Q code groupsApproximately 7 distinct HCPCS/J/Q code groups listed for bevacizumab and biosimilars

Biosimilars includedBiosimilar agents (Mvasi, Zirabev, Alymsys, Vegzelma, Jobevne, Avzivi, Avzivi/Avzivi-coded NOCs) are supported and included

Initial therapy criteria

General clinical approval criteria

Requests for listed bevacizumab agents may be approved if ANY of the following indication-specific criteria are met:

Ampullary adenocarcinoma (NCCN 2A)

Individual has a diagnosis of Ampullary adenocarcinoma
Bevacizumab is used in combination with a 5-fluorouracil-based (including capecitabine) regimen
Individual is using for a metastatic intestinal disease

Central Nervous System - Primary Tumor (Label, NCCN 2A)

Individual has a diagnosis of Central Nervous System - Primary Tumor

Continuation / maintenance therapy criteria

Continuation and maintenance therapy guidance

Maintenance: Bevacizumab used as maintenance therapy as a single agent when previously administered in first-line combination regimen; may be used until disease progression; not to be re-instituted after progression

Subsequent therapy if immunotherapy used first-line: Bevacizumab used as subsequent systemic therapy if immunotherapy was administered as first-line treatment in combination with pemetrexed and cisplatin or carboplatin; Bevacizumab used as subsequent systemic therapy for malignant peritoneal mesothelioma in combination with atezolizumab if individual has not previously been treated with immune checkpoint inhibitors

Continuation after erlotinib for NSCLC: As continuation of therapy following disease progression of erlotinib with bevacizumab for asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited progression (if T790M negative)

Unproven uses / exclusions

Operational exclusions and limited-use notes drawn from the criteria: bevacizumab is restricted to the disease/indication and regimen combinations listed in the clinical criteria (requests for other non-ophthalmologic uses are not approvable). For mesothelioma maintenance, bevacizumab may be used until progression but is not to be re-instituted after progression. Several tumor-specific criteria limit use to single-agent bevacizumab (e.g., meningiomas, certain CNS tumor uses, neurofibromatosis type 2 vestibular schwannomas) or to use in a single line of therapy. Safety/performance exclusions are operationalized: many indications require ECOG performance status 0-2 and absence of recent bleeding or thrombosis (mesothelioma), or no history of hemoptysis for NSCLC; Child-Pugh class requirements apply for HCC (Class A or B). Step therapy/ preferred-agent rules require trial/intolerance to preferred agents or current stabilization on a non-preferred agent before approving non-preferred biosimilars.

Applicable HCPCS / J / Q / ICD-10 codes

Covered HCPCS/J/Q codes for bevacizumab and biosimilarsHCPCS

J9035	Injection, bevacizumab, 10 mg [Avastin]
Q5107	Injection, bevacizumab-awwb, biosimilar, (Mvasi), 10 mg
Q5118	Injection, bevacizumab-bvzr, biosimilar, (Zirabev), 10 mg
Q5126	Injection, bevacizumab-maly, biosimilar, (Alymsys), 10 mg
Q5129	Injection, bevacizumab-adcd (Vegzelma), biosimilar, 10 mg
Q5160	Injection, bevacizumab-nwgd (Jobevne), biosimilar, 10 mg
J9999	Not otherwise classified, antineoplastic drugs [when specified as Avzivi (bevacizumab-tnjn)]
C9399	Unclassified drugs or biologicals [when specified as Avzivi (bevacizumab-tnjn)]

ICD-10 diagnosis codes (policy informational list)ICD-10

C17.0-C17.9	Malignant neoplasm of small intestine
C18.0-C20	Malignant neoplasm of colon, rectosigmoid junction, rectum
C21.2-C21.8	Malignant neoplasm of cloacogenic zone, overlapping sites of rectum, anus
C22.0	Liver cell carcinoma
C22.3	Angiosarcoma of 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-C34.92	Malignant neoplasm of bronchus and lung

1–10 of 37

1/4

HCPCS / J-codes historical/legacy codesHCPCS

J3490	Unclassified drugs (historically used for certain biosimilars; removed in some updates)
J3590	Unclassified biologics (historically used for certain biosimilars; removed in some updates)

Provider actions and billing rules

Prior Authorization

Prior authorization required with indication-specific criteria

Requests must meet the policy's indication-specific clinical criteria to be approved. Required documentation may include diagnosis, intended combination regimen, prior therapies, relevant biomarkers/mutations (for example pMMR/MSS, dMMR/MSI-H, POLE/POLD1, TMB), ECOG performance status, Child‑Pugh class where applicable, and prior immunotherapy eligibility/progression as described in the clinical criteria.

J9035
Q5107
Q5118
Q5126
Q5129
Q5160

Prior Authorization

Clinical evidence and guideline sources

Key evidence and guideline sources cited in the policy include randomized phase II/III trials and major guideline references. Trials and publications called out include Simkens 2015 (CAIRO3), Tewari 2014, Zalcman 2016, Ceresoli 2013, and trials such as AVAPERL, MAPS, AVANT, C-08, and NSGO-AVANOVA2. Multiple NCCN disease-specific guideline versions (2024/2025) are repeatedly referenced as the basis for many indication-specific recommendations.

Background and definitions

Background: Bevacizumab is a monoclonal antibody that binds and inhibits VEGF and is used across numerous non-ophthalmologic oncologic indications. The policy references FDA labeling and multiple NCCN recommendations, and it supports use of FDA‑approved biosimilars and extrapolation of biosimilar indications where scientifically justified. Several indications in the criteria require specific combination regimens, biomarker or mutation status (e.g., pMMR/MSS, dMMR/MSI-H, POLE/POLD1, TMB thresholds), ECOG and Child-Pugh performance classifications, or documentation of prior therapies per the approval nodes. This document is Part 1 of 2 of the full bevacizumab policy.

Term	Definition
{"text":"5FU-based","status":""},{"text":"A treatment regimen that includes fluorouracil (5-FU) or capecitabine.","status":""}
{"text":"ECOG performance status","status":""},{"text":"Scale (0-5) assessing individual's functional status; policy commonly requires 0-2.","status":""}
{"text":"pMMR/MSS","status":""},{"text":"Proficient mismatch repair / microsatellite-stable.","status":""}
{"text":"dMMR/MSI-H","status":""},{"text":"Deficient mismatch repair / microsatellite instability-high.","status":""}
{"text":"TMB","status":""},{"text":"Tumor mutational burden (mutations per megabase).","status":""}
{"text":"HRD","status":""},{"text":"Homologous recombination deficiency.","status":""}
{"text":"Preferred / Non-Preferred Agents","status":""},{"text":"Formulary placement varies by line of business and date; policy lists which bevacizumab products are preferred vs non-preferred for Commercial, Medicaid, and Medicare benefits.","status":""}

Revision history

03/01/2026revisedLatest

Step therapy table updates performed (most recent step therapy table update).

11/21/2025revised

Step therapy table updates and coding update: Removed Jobevne from HCPCS NOC C9399 and J9999 effective 12/31/25 and added Q5160 for Jobevne effective 1/1/26.

05/16/2025added

Jobevne (bevacizumab-nwgd) added to the criteria and the step therapy following FDA approval; coding review removed HCPCS J3490 and J3590 and added C9399 and J9999 for Avzivi and Jobevne at that time.

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria - Bevacizumab for Non-ophthalmologic Indications

Policy CodePolicy CC-0107

Change TypeStep therapy and coding updates (03/01/2026; historical updates)

Effective DateMar 1, 2026

Next Review Date

Key ActionRequests must meet the listed indication-specific clinical criteria and required documentation (prior therapies, biomarkers, ECOG/Child-Pugh status) for prior authorization.

SourceLink

On This Page

Individual has failed radiation therapy

Bevacizumab is used in a single line of therapy or as a single agent

Tumor types included

Adult medulloblastoma in combination with temozolomide and irinotecan
Adult intracranial and spinal ependymoma (excluding subependymoma) as a single agent only
IDH-mutant astrocytoma
Anaplastic glioma
Glioblastoma
Glioblastoma multiforme
High-grade glioma, recurrent
Meningiomas as a single agent only
Oligodendroglioma IDH-mutant, 1Q19 codeleted

Post-radiation CNS necrosis (NCCN 2A): Individual is using bevacizumab to treat symptomatic post-radiation necrosis of the central nervous system

Neurofibromatosis type 2 vestibular schwannomas (NCCN 2A): Bevacizumab as single agent treatment for neurofibromatosis type 2 vestibular schwannomas with hearing loss

Pediatric central nervous system cancers

Bevacizumab is part of treatment for recurrent or progressive pediatric CNS disease
Allowed pediatric regimens
- Used in combination for palliation in diffuse high-grade gliomas
- Used as part of TEMR (temozolomide, irinotecan, bevacizumab) regimen
- Used as part of MEMMAT (thalidomide, celecoxib, fenofibrate, etoposide, cyclophosphamide, bevacizumab) regimen

Advanced/metastatic colorectal, appendiceal, or anal adenocarcinoma (Label, NCCN 2A)

Individual has diagnosis of advanced or metastatic colorectal, appendiceal, or anal adenocarcinoma
Individual has not progressed on more than two lines of a bevacizumab-containing chemotherapy regimen (Simkens 2015)
Individual has either pMMR/MSS, dMMR/MSI-H, or POLE/POLD1 mutation with ultra-hypermutated phenotype (e.g. TMB >50 mut/Mb)
Individual is ineligible or has progressed on checkpoint inhibitor immunotherapy
ANY of the following
- Bevacizumab used in combination with 5-fluorouracil-based (including capecitabine) chemotherapy, irinotecan, or oxaliplatin
- Bevacizumab used in combination with trifluridine and tipiracil (Lonsurf) in patients who have progressed through standard therapies

Advanced/metastatic small bowel adenocarcinoma including ampullary adenocarcinoma (NCCN 2A)

Bevacizumab used in combination with 5-fluorouracil-based (including capecitabine) regimen
Bevacizumab used as initial therapy or subsequent therapy for disease progression
Bevacizumab used in a single line of therapy
Individual is pMMR/MSS

Vulvar cancer (NCCN 2A)

Option 1
- Bevacizumab used in combination with paclitaxel and cisplatin
- Bevacizumab used in a single line of therapy
Option 2 (PD-L1+ disease)
- Bevacizumab used in combination with pembrolizumab, paclitaxel, and a platinum agent for PD-L1 positive disease
- Bevacizumab and pembrolizumab may be continued as maintenance therapy

Cervical cancer (including vaginal cancer) (Label, NCCN 1, 2A)

Individual has persistent, recurrent, or metastatic disease
Bevacizumab is used in a single line of therapy
ANY of the following
- Bevacizumab used in combination with paclitaxel and either topotecan, cisplatin, or carboplatin for disease not amenable to curative surgery or radiotherapy (Tewari 2014)
- Bevacizumab used in combination with pembrolizumab, paclitaxel, and a platinum agent for PD-L1 positive disease
- Bevacizumab used as a single agent for second-line or subsequent therapy

Locally advanced/recurrent/metastatic cervical cancer with atezolizumab (NCCN 1): Bevacizumab used in combination with atezolizumab, a platinum-containing agent, and paclitaxel; or used in combination with atezolizumab for maintenance therapy

Small cell neuroendocrine carcinoma of the cervix (NECC) (NCCN 2A): Bevacizumab used in combination with paclitaxel and topotecan

Endometrial carcinoma (NCCN 2A)

Individual has advanced or recurrent disease
Bevacizumab used in combination with carboplatin and paclitaxel
Following combination therapy, bevacizumab used as single-agent maintenance therapy until disease progression or prohibitive toxicity

Malignant pleural or peritoneal mesothelioma (NCCN 1, 2A)

Bevacizumab used as first-line therapy for unresectable malignant pleural mesothelioma or peritoneal mesothelioma
Used in combination with pemetrexed and either cisplatin or carboplatin
Individual has ECOG performance status 0-2 and no history of bleeding or thrombosis (Zalcman 2016, Ceresoli 2013)
Individual is not eligible for surgery

Mesothelioma additional uses

Maintenance: Bevacizumab used as maintenance therapy as a single agent when previously administered in first-line combination regimen; may be used until disease progression; not to be re-instituted after progression
Subsequent therapy if immunotherapy used first-line: Bevacizumab used as subsequent systemic therapy if immunotherapy was administered as first-line treatment in combination with pemetrexed and cisplatin or carboplatin; or used as subsequent systemic therapy for malignant peritoneal mesothelioma in combination with atezolizumab if individual has not previously been treated with immune checkpoint inhibitors

Non-squamous NSCLC with EGFR mutation (NCCN 2A)

Diagnosis of recurrent, advanced, or metastatic non-squamous NSCLC
ECOG performance status 0-2 and no history of hemoptysis
EGFR positive mutation
Bevacizumab used in combination with erlotinib
ANY of the following
- As first-line therapy
- As continuation of therapy following disease progression of erlotinib with bevacizumab for asymptomatic disease, symptomatic brain lesions, or symptomatic systemic limited progression (if T790M negative)

Advanced/recurrent/metastatic non-squamous NSCLC (Label, NCCN 1, 2A)

Diagnosis of advanced, recurrent, or metastatic non-squamous NSCLC
ECOG performance status 0-2 and no history of hemoptysis
Bevacizumab used in combination with platinum-based therapy and either a taxane or pemetrexed
ANY of the following
- As first-line therapy (Label)
- As subsequent therapy if disease progressed during or following treatment with a targeted agent for the expressed oncogene

NSCLC second-line or subsequent single agent (NCCN 1): Diagnosis of advanced, recurrent, or metastatic non-squamous NSCLC; ECOG 0-2 and no history of hemoptysis; Bevacizumab used as second-line or subsequent therapy as a single agent

NSCLC maintenance therapy (NCCN 1): Bevacizumab used as maintenance therapy for advanced, recurrent, or metastatic non-squamous NSCLC; Bevacizumab was previously administered as part of a first-line combination chemotherapy regimen; Bevacizumab used as single agent, or in combination with pemetrexed or atezolizumab; May be used until disease progression

Epithelial ovarian, fallopian tube, or primary peritoneal cancer (stage II-IV) - adjuvant/maintenance (NCCN 1, 2A): Diagnosis of stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer; Bevacizumab used in combination with other chemotherapy following initial surgical resection (adjuvant); Bevacizumab used as maintenance therapy as a single agent

Epithelial ovarian, fallopian tube, or primary peritoneal cancer - maintenance or combination (NCCN 1, 2A): Bevacizumab used as maintenance therapy for advanced, recurrent, or metastatic disease; previously administered as part of a combination chemotherapy regimen; May be used until disease progression; Used as a single agent

Bevacizumab + olaparib maintenance (NCCN 1, 2A, Lynparza label): Individual achieved CR or PR to primary therapy AND (Deleterious germline and/or somatic BRCA 1/2 mutation confirmed OR Genomic instability (HRD positive status))

Bevacizumab with atezolizumab for ovarian cancer (NCCN 1, 2A): Individual does not have contraindications to PD-1/PD-L1 inhibitors; Bevacizumab used in combination with platinum-based therapy, a taxane, and atezolizumab; Use as first-line for PD-L1 ≥ 1% tumors or as subsequent therapy after targeted agent progression

Recurrent/metastatic ovarian disease options: Bevacizumab used as a single agent or in combination with other chemotherapy for relapsed/metastatic disease; Used as maintenance therapy as a single agent; Used in combination with mirvetuximab soravtansine-gynx for FRα-expressing tumor for recurrent or platinum-resistant persistent disease; Used in combination with other chemotherapy for platinum-resistant persistent disease (except ixabepilone)

Hepatocellular carcinoma (Label, NCCN 1): Individual has advanced, unresectable, or metastatic HCC; Using in combination with atezolizumab as first-line treatment or subsequent-line systemic therapy; Individual has Child-Pugh Class A or B liver function; Individual has ECOG performance status 0-2; Bevacizumab may be used until disease progression

Renal cell carcinoma (RCC)

Metastatic RCC (Label): Individual has metastatic RCC and bevacizumab used in combination with interferon alpha 2
Relapsed/unresectable stage IV non-clear cell RCC (NCCN 2A): Bevacizumab used as single agent in non-clear cell histology OR used in combination with erlotinib or everolimus in non-clear cell histology

Soft tissue sarcoma (NCCN 2A): Bevacizumab used as single agent for angiosarcoma OR used in combination with temozolomide for solitary fibrous tumor

NSCLC maintenance use: Bevacizumab used as maintenance therapy for advanced, recurrent, or metastatic non-squamous NSCLC when previously administered as part of a first-line combination regimen; may be used as single agent or with pemetrexed or atezolizumab; may be used until disease progression

Use until disease progression or prohibitive toxicity: Where specified (e.g., endometrial carcinoma, mesothelioma, HCC, ovarian maintenance, NSCLC maintenance), bevacizumab may be continued as maintenance until disease progression or prohibitive toxicity

Continuation-specific thresholds

ECOG continuation thresholdECOG performance status 0-2 for continued/ongoing therapy

Child-Pugh continuation thresholdChild-Pugh class A or B required in HCC when using bevacizumab with atezolizumab

TMB continuation exampleTMB >50 mut/Mb cited as example of ultra-hypermutated phenotype in colorectal/related cancers

Duration noteMay be used as maintenance or continued until disease progression or prohibitive toxicity where specified

Step therapy and prior authorization applicable

Step therapy and prior authorization processes apply per the policy. The step therapy tables were updated most recently on 03/01/2026; providers must follow plan- and line-of-business–specific PA and step therapy requirements and the listed preferred/non-preferred agent rules when requesting bevacizumab or biosimilars.

J9035
Q5107
Q5118
Q5126
Q5129
Q5160
C9399
J9999

Billing Rule

Use of appropriate HCPCS/J/Q code

Report the specific HCPCS/J/Q code for the bevacizumab product actually administered. The policy notes removal of legacy unclassified codes (J3490/J3590) in updates and instructs use of product-specific codes or the appropriate NOC when specified.

J9035
Q5107
Q5118
Q5126
Q5129
Q5160
C9399
J9999

Step Therapy

Step therapy / preferred agent requirement

A preferred bevacizumab or biosimilar agent list is maintained. Requests for non-preferred agents require documentation of a trial and intolerance to one preferred agent, or that the member is currently stabilized on the requested non-preferred agent per the step therapy requirements.

Documentation Required

Biosimilar extrapolation and indication documentation

When approving a biosimilar for an indication, document the scientific justification for extrapolation consistent with FDA principles (considering mechanism of action, pharmacokinetics, biodistribution, immunogenicity, and expected toxicities). The plan may also impose additional preferred-agent requirements.

Documentation Required

Diagnosis coding

Ensure ICD-10 diagnosis code(s) that support the requested indication are submitted with the claim.

See the policy's ICD-10 diagnosis code list (e.g., C17.0-C17.9, C18.0-C20, C22.0, C34.00-C34.92, C71.0-C71.9, etc.)

2019-2025 (multi-year)revised

Multiple historical updates across 2019–2025 clarified indications, added biosimilars (Avzivi, Avzivi additions, Vegzelma, Zirabev, Alymsys), updated NCCN-based uses (CNS cancers including NF2 vestibular schwannomas, pediatric CNS uses, colorectal mutation-specific guidance, ovarian cancer combinations, mesothelioma), and repeatedly updated step therapy and coding tables.