CurrentAnthemPolicy CC-0107

Medical Drug Clinical Criteria - Bevacizumab for Non-ophthalmologic Indications

Defines clinical coverage criteria, step-therapy and biosimilar use, and coding guidance for bevacizumab (Avastin) and listed biosimilars for non-ophthalmologic oncologic and related indications. Excludes intraocular/ophthalmologic uses.

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria - Bevacizumab for Non-ophthalmologic Indications

Policy CodePolicy CC-0107

Change TypeCoding & criteria updates (biosimilar additions, step therapy revisions)

Effective Date03/01/2026

Next Review DateN/A

Key ActionRequests for Avastin or listed biosimilars must meet the indication-specific medical necessity criteria listed (diagnosis, combinations, prior therapy status, biomarkers, ECOG/Child-Pugh where specified) to be approved.

SourceLink

POLICY UPDATE CHANGES

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

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

Multiple dates 2022-2026 - Ongoing step therapy table updates and coding revisions including additions/removals of HCPCS/J-codes and ICD-10 codes.

MultipleCovered Indications (FDA and off-label per NCCN)

ListedBiosimilars included

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.

Coverage Summary & Scope

This policy defines coverage for bevacizumab (Avastin) and listed biosimilars (Alymsys, Avzivi, Jobevne, Mvasi, Vegzelma, Zirabev) for a broad set of non-ophthalmologic oncologic and related indications, aligning coverage with FDA-labeled oncology indications and NCCN guideline recommendations. The policy expressly excludes intraocular/ophthalmologic uses of bevacizumab. Biosimilars are considered appropriate for the same indications as the reference product and may be used for extrapolated indications when supported by FDA approval and sufficient scientific rationale. Effective date: 2026-03-01. Payer/policy metadata: Document # CC-0107; Status: Revised; Last review: 05/16/2025; Benefit lines include Commercial, Medicaid, and Medicare medical benefits with plan- and state-specific step therapy and preferred agent lists.

Key thresholds & quick facts

ECOG Performance Status requirementMany indications require ECOG 0-2

Child-Pugh class for HCCChild-Pugh Class A or B required for HCC uses

Ultra-hypermutated phenotype thresholdTumor mutational burden >50 mut/Mb (example for ultra-hypermutated phenotype)

Named bevacizumab agents/biosimilars count7 agents listed (Avastin, Alymsys, Avzivi, Jobevne, Mvasi, Vegzelma, Zirabev)

Policy effective date2026-03-01

Policy numberDocument # CC-0107

General Approvable Criteria (Initial / Indication-specific)

Covered when ALL of the following are met for initial therapy or indication-specific use, as detailed below. Documentation of diagnosis, prior therapies, performance status, and relevant contraindications must be submitted.

ALL of the following

General Coding and Agents
- Requested agent is bevacizumab (Avastin) or an FDA-licensed biosimilar: Alymsys, Avzivi, Jobevne, Mvasi, Vegzelma, or Zirabev.
- Appropriate HCPCS/NDC coding corresponds to the selected bevacizumab product and billing reflects vial sizes and units administered (submit drug name, dose, vial size, NDC when available).
- Provider attests that intraocular/ophthalmologic indications are NOT being treated under this request (ophthalmologic uses are excluded from this policy).

Not Approvable / Exclusions

Requests may not be approved for the following uses:

ANY of the following

General exclusions: All other non-ophthalmologic indications not included above
Colon adjuvant exclusion: Adjuvant therapy following surgery for stage II or III adenocarcinoma of the colon
Irinotecan combination exclusion: Bevacizumab in combination with the same irinotecan-based regimen that was previously used in combination with ziv-aflibercept
Concomitant targeted biologics exclusion:

Step Therapy / Non-preferred Agent Requirements

Step therapy, preferred agent designations, and effective dates vary by line of business and by state. Commercial and Medicare medical benefits identify Avastin and Mvasi as preferred agents with other biosimilars listed as non-preferred at various effective dates; Medicaid preferred/non-preferred lists and effective dates differ by state. Providers must follow plan-specific step therapy tables and prior authorization processes and also adhere to state-specific Medicaid formularies and effective dates when applicable.

Prior Authorization, Documentation & Billing Requirements

Prior Authorization

Clinical criteria-based prior authorization required

Requests for bevacizumab (Avastin) and biosimilars require clinical criteria–based prior authorization. The request must document that the indication-specific medical necessity criteria are met, including diagnosis, required combination regimens (when applicable), prior therapies, relevant biomarkers, and functional/liver status.

Affected HCPCS/Q-codes: J9035 and biosimilar Q-codes (see billing callouts below).
Clinical documentation must show indication-specific criteria: diagnosis, prior lines of therapy, combinations, biomarkers, ECOG/Child-Pugh where required.

Step Therapy

Step therapy for non-preferred agents

Step therapy requirements may apply when a non-preferred bevacizumab agent is requested. Prior authorization may require documentation that the member has had an adequate trial of preferred agent(s) or intolerance/contraindication to preferred agents, or that the member is currently stable on a non-preferred agent and switching is not clinically appropriate.

Applicable Codes

Primary HCPCS/J-codes for bevacizumab and biosimilars (billing codes listed in policy)HCPCS

J9035	Injection, bevacizumab, 10 mg [Avastin]
J9999	Not otherwise classified, antineoplastic drugs [when specified as Avzivi (bevacizumab-tnjn)]
C9399	Unclassified drugs or biologicals [when specified as Avzivi (bevacizumab-tnjn)]
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

HCPCS / J-codes / Q-codes (drug administration)HCPCS|mixed

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 (examples listed)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 23

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HCPCS NOC codes historically referenced/changedHCPCS

C9142	Previously used for Alymsys (removed in later updates)
J3490	Drug, unidentified (historical coding references removed in later updates)
J3590	Unclassified biologics (historical references removed in later updates)

Diagnosis codes (ICD-10) referenced by policyICD-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

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Clinical Evidence & Guideline References

AVANT, MAPS, CAIRO3, AVAPERL, othersKey RCTs and trials cited (AVANT, MAPS, CAIRO3/Simkens 2015, AVAPERL, Tewari 2014, Ray‑Coquard 2019)

NCCN coverage across tumor typesNCCN guideline–based uses listed (CNS, colorectal, HCC, mesothelioma, ovarian, NSCLC, small bowel, cervical, vulvar, vaginal, renal, soft tissue sarcoma, pediatric CNS) up to 2025

Jobevne added 05/16/2025Jobevne (bevacizumab‑nwgd) added to criteria and step therapy following FDA approval (05/16/2025); coding/Q‑code updates noted

Key clinical evidence cited in the policy informs indication-specific approvals: the CAIRO3 trial (Simkens 2015) supports continuation/maintenance bevacizumab strategies in colorectal cancer; Tewari 2014 underlies approval for persistent, recurrent, or metastatic cervical cancer in combination regimens; Zalcman 2016 and Ceresoli 2013 support use in mesothelioma in patients with ECOG 0-2 and no bleeding/thrombosis; Ray-Coquard 2019 supports bevacizumab combined with olaparib for maintenance in ovarian cancer, particularly in BRCA/HRD-defined populations. NCCN guideline recommendations through 2025 are used to expand and align off-label, guideline-based uses (CNS, small bowel/ampullary, HCC, ovarian, pediatric CNS, among others) and are explicitly referenced in policy criteria.

Background & Definitions

Background: the policy addresses use of Avastin (bevacizumab) and named biosimilars for non-ophthalmologic oncologic indications, aligning coverage with FDA labels and NCCN guidance. Biosimilars that demonstrate FDA biosimilarity share approved uses with the reference product and may be extrapolated to other indications when scientifically justified and supported by FDA approval. The policy therefore treats biosimilars as interchangeable for approved and extrapolated indications consistent with FDA and NCCN positions.

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 patient functional status; many indications require 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":"HRD","status":""},{"text":"Homologous recombination deficiency, includes but is not limited to BRCA mutations.","status":""}
{"text":"Preferred Agents","status":""},{"text":"Products preferred by the plan for step therapy and formulary placement (e.g., Avastin, Mvasi for many lines of business as listed).","status":""}
{"text":"Non-Preferred Agents","status":""},{"text":"Products not preferred by the plan; may be subject to step therapy or additional requirements.","status":""}

Document History

05/16/2025added

Jobevne (bevacizumab-nwgd) added to the policy criteria and step therapy following FDA approval; NCCN updates added uses in CNS cancer including NF2 vestibular schwannomas and pediatric CNS cancers and added specific mutation indications for colorectal, appendiceal, anal, small bowel cancers; coding reviewed with additions/removals of several HCPCS and ICD-10 codes.

11/21/2025coding_update

Coding update: Removed Jobevne from HCPCS NOC C9399 and J9999 effective 12/31/2025 and added Q5160 for Jobevne effective 01/01/2026; step therapy table updates on same date.

2019-2026administrative_updates

Multiple administrative and clinical updates recorded across document history (step therapy table updates, coding revisions, additions/removals of HCPCS/J/Q codes and ICD-10 codes) from 2019 through 03/01/2026, including recurring step therapy adjustments and biosimilar additions.

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria - Bevacizumab for Non-ophthalmologic Indications

Policy CodePolicy CC-0107

Change TypeCoding & criteria updates (biosimilar additions, step therapy revisions)

Effective Date03/01/2026

Next Review DateN/A

SourceLink

On This Page

Step Therapy / Preferred vs Non-preferred Agents

When a formulary step-therapy requirement exists, the prescriber has either tried and failed the preferred first-line systemic therapy for the diagnosis OR documents a medical reason (contraindication/intolerance) why the preferred agent cannot be used.
For indications where bevacizumab plus another systemic agent is guideline-recommended, authorization must reflect the combination regimen (both agents), or documentation must support why bevacizumab is used as monotherapy (e.g., maintenance, intolerance to cytotoxic chemotherapy).
Biosimilar substitution is acceptable unless a medical exception is documented; requests for a specific branded product require supporting clinical rationale.

Diagnosis Codes Associated with Policy

Clinical documentation must include an ICD-10 diagnosis code consistent with an approved non-ophthalmologic indication (examples include but are not limited to): K63.1 (Malignant neoplasm of appendix) when treated per colon guidelines for appendiceal adenocarcinoma; C18–C20 series (colon/rectal malignancies) for metastatic colorectal cancer; C71.x (brain) or other CNS neoplasm codes for high-grade glioma/glioblastoma; C34.x (lung) for non-squamous NSCLC; C56.x/C57.x (ovarian/fallopian tube/primary peritoneal) for epithelial ovarian cancer; C22.0 (hepatocellular carcinoma); C64.x (renal cell carcinoma); C45.x (mesothelioma); C51–C58 (cervical/vaginal/vulvar/endometrial malignancies); C41.x–C49.x for soft tissue sarcomas including angiosarcoma; C17.x (small intestine) for small bowel adenocarcinoma; and appropriate pediatric CNS/neoplasm codes for pediatric indications.
Submit documentation of tumor histology, stage (metastatic/unresectable), and prior lines of systemic therapy (agents, dates, responses) to support the selected ICD-10 code and the medical necessity of bevacizumab.

General Approvable Criteria

Central Nervous System (CNS) cancers
- High-grade (WHO Grade III/IV) gliomas (including glioblastoma/glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma) for recurrent disease or when recommended by NCCN after radiation therapy failure.
- Meningioma in selected circumstances per NCCN (single-agent bevacizumab) or for symptomatic management of radiation necrosis of the CNS.
Colorectal and Related (including small bowel, ampullary, appendiceal)
- Metastatic colorectal cancer in combination with 5-fluorouracil–based chemotherapy, irinotecan, or oxaliplatin for first-line or subsequent-line therapy; continuing bevacizumab after progression on a bevacizumab-containing regimen is acceptable per guidelines.
- Small bowel adenocarcinoma and ampullary adenocarcinoma treated per colon cancer regimens in combination with 5-fluorouracil–based therapy.
Ovarian / Fallopian Tube / Primary Peritoneal Cancer
- Epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with approved chemotherapy regimens and as bevacizumab monotherapy maintenance until progression when indicated by FDA/NCCN guidance.
- Adjuvant therapy post-surgical resection in combination with chemotherapy when indicated; maintenance combinations with PARP inhibitors (e.g., olaparib) in patients with BRCA mutation or HRD-positive disease per guideline categories are approvable when eligibility criteria are met.
Non–Small Cell Lung Cancer (NSCLC)
- Unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC in combination with platinum-based chemotherapy regimens (e.g., carboplatin + paclitaxel or pemetrexed-containing regimens) or with atezolizumab + carboplatin + paclitaxel as appropriate per NCCN, in patients without contraindications such as recent hemoptysis.
- Use with targeted agents (e.g., erlotinib) in EGFR-mutated disease as recommended by guidelines when appropriate.
Hepatocellular Carcinoma (HCC)
- Unresectable or metastatic HCC in combination with atezolizumab for systemic first-line therapy in patients without prior systemic therapy and with appropriate liver function (Child-Pugh A/B as applicable to guideline populations).
- Subsequent-line use allowed per NCCN guidance when clinically appropriate.
Renal Cell Carcinoma (RCC)
- Metastatic RCC in combination with interferon-alpha or as single agent/combination per NCCN for non–clear cell histologies; use with everolimus or erlotinib in specified non–clear cell situations is approvable when supported by pathology and prior therapy data.
Mesothelioma (Pleural and Peritoneal)
- Unresectable malignant pleural mesothelioma in combination with pemetrexed plus cisplatin or carboplatin as first-line therapy, with single-agent bevacizumab maintenance until progression when indicated and patient meets eligibility (ECOG 0–2, no active bleeding or thrombosis).
- Peritoneal mesothelioma: pemetrexed + cisplatin + bevacizumab as a preferred option in patients not eligible for surgery; subsequent-line regimens per NCCN when prior immunotherapy exposure is considered.
Cervical, Vulvar, Vaginal, Endometrial Malignancies
- Persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel and topotecan or paclitaxel with platinum agents; combinations with pembrolizumab (where FDA-approved) plus chemotherapy and bevacizumab are approvable per labeling and NCCN.
- Advanced or recurrent endometrial, vulvar, or vaginal malignancies per NCCN recommendations when used in combination regimens or as single-agent therapy for disease progressed on cytotoxic chemotherapy when supported by trial evidence or guideline category.
Soft Tissue Sarcoma
- Angiosarcoma: single-agent bevacizumab as recommended by NCCN for vascular sarcomas.
- Selected soft tissue sarcomas (e.g., solitary fibrous tumor) in combination with temozolomide when recommended by guidelines or tumor board consensus and supported by documentation.
Pediatric CNS and Other Pediatric Indications
- Use in pediatric CNS tumors or other pediatric oncology indications recommended by pediatric oncology guidelines or NCCN pediatric considerations; require pediatric oncology specialist documentation, dosing per weight/age, and rationale for bevacizumab over alternative standard therapies.

ALL of the following

Clinical exclusions: bevacizumab is not covered for ophthalmologic/intravitreal uses under this policy; not covered when contraindications are present without documented mitigation (e.g., recent major surgery, uncontrolled hypertension, active clinically significant bleeding, significant thromboembolic events).
Exclusion examples are illustrative; evaluate individual clinical context.
Provider must document ECOG/WHO performance status, relevant laboratory data (e.g., renal/hepatic function, coagulation), and any prior hemorrhagic or thrombotic complications to support safe use.

Documentation Required

Biomarker and prior therapy documentation

Provide biomarker and prior therapy information with the authorization request. Include lab/pathology reports or clinical notes supporting the biomarkers and prior systemic treatments.

Mismatch repair (MMR) / microsatellite instability (MSI) status when relevant to the indication.
POLE and POLD1 mutation status when relevant.
Tumor mutational burden (TMB) when relevant.
Documentation of prior checkpoint inhibitor (ICI) use and response (agent, dates, reason for discontinuation).
Number of prior bevacizumab-containing regimens and dates of exposure.

Documentation Required

Performance status and liver function documentation

Document performance status and hepatic function where required by the indication. Include objective scores or recent clinic notes.

Eastern Cooperative Oncology Group (ECOG) Performance Status for mesothelioma and NSCLC (document ECOG 0–2 where NCCN criteria require).
Child-Pugh classification for hepatocellular carcinoma (document Class A or B when supporting use per NCCN/FDA).

Billing Rule

Use specified HCPCS/J/Q codes

Use the specified HCPCS and Q-codes when billing bevacizumab products. The claim must report the HCPCS/Q-code that corresponds to the specific product administered.

Report J9035 for bevacizumab (Avastin) when billing the reference product.
Report the appropriate Q-code for biosimilar products (see examples below).
Ensure the product-specific code is used on the claim to avoid denials or misclassification.

Prior Authorization

Step therapy / prior authorization applies

Plan-specific step therapy and prior authorization rules apply. Providers must follow the member’s plan table for step therapy requirements. Coverage rules and step therapy lists are updated periodically; see Document History for recent changes.

Follow the plan-specific step therapy tables for the member’s benefit.
Authorization decisions may change as step therapy lists are updated; refer to the policy Document History for revisions.

Documentation Required

Use guideline-aligned indication documentation

When requesting authorization, reference guideline-aligned indication support (FDA label, NCCN) in the clinical rationale. Attach relevant excerpts or clinical notes that map the patient to the labeled or guideline-supported criteria.

Cite the FDA label or specific NCCN guideline section supporting the requested use.
Attach clinic notes, pathology, or imaging that document the patient meets the guideline/FDA criteria.

Billing Rule

Bill correct HCPCS/Q-code for specific biosimilar

Bill the correct HCPCS or Q-code that corresponds to the exact biosimilar product administered. DO NOT report generic or deprecated NOC codes. Using the correct product-specific code ensures accurate product identification and avoids payment or audit issues.

Examples: Q5107 – bevacizumab-bvzr (Mvasi).
Q5160 – bevacizumab-jvfs (Jobevne).
Report J9035 for the reference product Avastin when billed as the reference biologic.
Avoid reporting unspecified or deprecated NOC codes; always use the product-specific HCPCS or Q-code for the administered biologic/biosimilar.