CurrentCentenePolicy CP.PHAR.93

Bevacizumab (Alymsys, Avastin, Mvasi, Vegzelma, Zirabev) (PDF)

Defines medical necessity, initial and continuation criteria, approved FDA and selected off-label indications, step-therapy redirection to preferred biosimilars, dosing limits, approval durations, dose rounding guidance, and coding implications for bevacizumab and listed biosimilars for Centene lines of business (Commercial, HIM, Medicaid).

Policy Summary

PayerCentene

PolicyBevacizumab (Alymsys, Avastin, Mvasi, Vegzelma, Zirabev) (PDF)

Policy CodePolicy CP.PHAR.93

Change TypeUpdates to indications, biosimilars, HCPCS codes, and approval durations

Effective DateDec 1, 2011

Next Review Date

Key ActionProvider must submit documentation (office notes, labs or other clinical information) supporting that the member has met all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Multiple historical updates listed (addition of biosimilars, NCCN-supported regimens, appendix updates, HCPCS code updates) with dates across 2021-2023.

Commercial approval duration revised to 12 months or duration of request, whichever is less.

Added HCC indication in combination with atezolizumab/Tecentriq and dosing.

Added multiple NCCN-supported indications (e.g., ampullary adenocarcinoma, malignant peritoneal mesothelioma, pediatric diffuse high-grade glioma) in 4Q2022 review.

Updated HCPCS coding: added Q5126 and later Q5129 and Q5160; removed C9142.

Added biosimilars (Vegzelma, Avzivi, Jobevne, others) to policy as FDA approvals occurred.

4Q2023 and 4Q2024 annual reviews revised numerous oncology indication criteria per NCCN (NSCLC, RCC, ovarian, HCC, CRC, cervical cancer).

4Q2025 annual review: added step therapy bypass for IL HIM per IL HB 5395 and extended initial approval duration for Medicaid and HIM from 6 to 12 months for maintenance medication.

Updated Appendix E to include Oklahoma, Mississippi, Tennessee, Indiana at various dates.

Added additional off-label oncology uses and required combination therapy in some off-label contexts (e.g., ampullary adenocarcinoma, mesothelioma, small bowel adenocarcinoma, vulvar cancer).

Ophthalmology uses clarified to remove age restriction and require ophthalmologist prescriber; added radiation retinopathy and retinopathy of prematurity.

7FDA-approved indications listed

16Off-label adult oncology indications

2Pediatric off-label indications

12Approval duration (months)

4HCPCS/Q-code changes noted

>=2022Revision history timeframe

Coverage Summary & Scope

coverage_stance: covered_with_criteria. This policy covers bevacizumab (Avastin) and listed biosimilars for specified FDA-approved oncology indications and selected NCCN-supported off-label uses, with biosimilar redirection rules, dosing limits, and intravitreal-specific ophthalmology restrictions.

scope_summary: Defines medical necessity, initial and continuation criteria, approved FDA and selected off-label indications, step-therapy redirection to preferred biosimilars (Mvasi or Zirabev), dosing limits including oncology maximums and intravitreal limits, approval durations, dose rounding guidance, and coding implications for Centene lines of business (Commercial, HIM, Medicaid).

brief summary of what the policy covers: Bevacizumab and multiple biosimilars are VEGF-specific angiogenesis inhibitors indicated for several cancers (metastatic CRC, unresectable non-squamous NSCLC, recurrent glioblastoma, metastatic RCC, persistent/recurrent/metastatic cervical cancer, epithelial ovarian/fallopian tube/primary peritoneal cancer, and HCC with atezolizumab). Policy also authorizes selected NCCN-supported off-label adult and pediatric oncology uses and ophthalmology intravitreal uses (nAMD, DME, RVO, DR, neovascular glaucoma, choroidal neovascularization, radiation retinopathy, ROP). Biosimilar redirection requires use of Mvasi or Zirabev for requests for Alymsys, Avastin, Avzivi, Jobevne, or Vegzelma unless contraindicated or adverse effects occur. Oncology dosing is limited to 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks unless supported by guidelines or literature. Ophthalmology requests must be for intravitreal bevacizumab formulation only with a per-dose limit of ≤ 2.5 mg (typical intravitreal regimens 1.25 mg q4 weeks; ROP dosing example 0.2 mg).

I. Initial Approval Criteria - FDA-Approved Indications

Covered when ALL of the following are met:

ALL of the following

Diagnosis of one of the following: metastatic colorectal cancer (CRC); non-squamous non-small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); persistent, recurrent, or metastatic cervical cancer; epithelial ovarian, fallopian tube, or primary peritoneal cancer; hepatocellular carcinoma (HCC).
Prescribed by or in consultation with an oncologist.
Age ≥ 18 years.
Indication-specific regimen/criteria (must meet the listed criteria for the specific diagnosis)
- For CRC: disease is advanced, metastatic, or unresectable, and prescribed in combination with one of: 5-FU/leucovorin or capecitabine-based chemotherapy; IROX (irinotecan and oxaliplatin); FOLFOX or CapeOX; irinotecan or FOLFIRI; FOLFIRINOX; or Lonsurf if previously progressed through all available regimens.

I. Initial Approval Criteria - Oncology Non‑FDA‑Approved Adult Indications (off‑label)

I. Initial Approval Criteria - Oncology Non‑FDA‑Approved Pediatric Indications

I. Initial Approval Criteria - Ophthalmology Indications (intravitreal only)

II. Continued Therapy (All Indications in Section I)

III. Diagnoses / Indications Not Authorized

III. Diagnoses/Indications Not Authorized

Not authorized - single node: Non‑FDA approved indications not addressed in this policy are not covered unless sufficient documentation of efficacy and safety is provided per off-label use policies or evidence of coverage documents

Refer to off-label use policies: CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid)

Provider Actions & Prior Authorization Requirements

Prior Authorization

Documentation required

Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.

Documentation required

Prior Authorization

Biosimilar step therapy / redirection

For requests for Alymsys, Avastin, Avzivi, Jobevne, or Vegzelma, member must use Mvasi or Zirabev unless both are contraindicated or clinically significant adverse effects are experienced; prior authorization may be required for Mvasi and Zirabev.

Biosimilar step therapy / redirection

Applicable Codes

HCPCS / J-code covered formulations (informational)HCPCSCovered

J9035	Injection, bevacizumab, 10 mg
C9257	Bevacizumab, per 10 mg (hospital outpatient only)
Q5107	Bevacizumab-awwb, biosimilar, 10 mg
Q5118	Bevacizumab-adcd, biosimilar, 10 mg
Q5126	Bevacizumab-bvzr, biosimilar, 10 mg
Q5129	Bevacizumab-maly, biosimilar, 10 mg
Q5160	Bevacizumab-nwgd, biosimilar, 10 mg
J9999	Not otherwise classified, antineoplastic drug (used informationally)

ICD-10-CM Diagnosis Codes that Support Coverage CriteriaICD-10Covered

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

1–10 of 34

1/4

Historical/current HCPCS Q-codes referenced in updatesHCPCS

C9142	Bevacizumab, 10 mg (historical Q-code)
Q5126	Bevacizumab-bvzr, biosimilar, 10 mg
Q5129	Bevacizumab-maly, biosimilar, 10 mg
Q5160	Bevacizumab-nwgd, biosimilar, 10 mg

Clinical Evidence & References

Primary FDA prescribing information and biosimilar PIs referenced: Avastin Prescribing Information (Sept 2022) and multiple biosimilar prescribing information documents (Mvasi PI June 2025; Zirabev PI Aug 2024; Alymsys PI Apr 2022; Vegzelma PI Feb 2023; Avzivi PI Dec 2023; Jobevne PI Apr 2025).

Guideline sources: National Comprehensive Cancer Network (NCCN) Drugs & Biologics Compendium and disease-specific NCCN guidelines cited, including CNS Cancers v1.2025, Ovarian Cancer v3.2025, Cervical Cancer v4.2025, Hepatocellular Carcinoma v1.2025, Kidney Cancer v1.2026, and NSCLC v7.2025.

Dose rounding reference: Hematology/Oncology Pharmacy Association (HOPA) position statement on dose rounding (2018).

Background & Definitions

Background summary: Bevacizumab and multiple biosimilars are VEGF-specific angiogenesis inhibitors indicated across several malignancies and used off-label in NCCN-supported settings. FDA-approved indications include metastatic colorectal cancer, unresectable non-squamous NSCLC, recurrent glioblastoma, metastatic RCC, persistent/recurrent/metastatic cervical cancer, epithelial ovarian/fallopian tube/primary peritoneal cancer, and HCC in combination with atezolizumab.

Biosimilars have been added to the policy as FDA approvals occurred (examples include Mvasi, Alymsys, Vegzelma, Avzivi, Jobevne, Zirabev) and prescribing information for these products are cited in the policy references.

The policy includes biosimilar redirection/step therapy where requests for certain branded/biosimilar products (Alymsys, Avastin, Avzivi, Jobevne, Vegzelma) generally must use Mvasi or Zirabev unless contraindicated or clinically significant adverse effects occur, with state-specific exceptions noted (Appendix E and IL HB 5395).

Dosing and formulation guidance: oncology IV maximums align with FDA labeling (15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks), dose rounding guidance provided in Appendix F, and ophthalmology uses are restricted to intravitreal bevacizumab solution only with a per-dose limit of ≤ 2.5 mg (typical intravitreal 1.25 mg q4 weeks; ROP example dosing 0.2 mg).

Definitions (short glossary):

• NCCN: National Comprehensive Cancer Network (policy references NCCN compendia and specific guideline versions 2024–2026).

• 5-FU: fluorouracil (used in CRC regimens).

• IROX: irinotecan and oxaliplatin (combination chemotherapy referenced for CRC).

Revision History & Policy Changes

08.15.21annual_review

4Q2021 annual review: added NCCN-supported regimens/classifications for CRC, NSCLC, glioblastoma, cervical and ovarian cancers; added Child‑Pugh A criterion for HCC; added low‑grade WHO grade I glioma to off‑label indications; added Nevada to Appendix E; allowed bypass of redirection to preferred agent if state regulations prohibit redirection.

12.10.21rt_update

RT4 update: Mvasi FDA‑approved indications for epithelial ovarian/fallopian tube/primary peritoneal cancers were added to the policy.

01.20.22policy_revision

Commercial approval duration revised to 12 months (or duration of request, whichever is less) for bevacizumab and biosimilars (changed from length of benefit).

Policy Summary

PayerCentene

PolicyBevacizumab (Alymsys, Avastin, Mvasi, Vegzelma, Zirabev) (PDF)

Policy CodePolicy CP.PHAR.93

Change TypeUpdates to indications, biosimilars, HCPCS codes, and approval durations

Effective DateDec 1, 2011

Next Review Date

Key ActionProvider must submit documentation (office notes, labs or other clinical information) supporting that the member has met all approval criteria.

SourceLink

On This Page

For non-squamous NSCLC: disease is unresectable, recurrent, advanced, or metastatic, and prescribed as single-agent therapy or in combination with carboplatin + paclitaxel; with pemetrexed ± carboplatin/cisplatin; with atezolizumab (Tecentriq) ± carboplatin + paclitaxel; or with erlotinib for sensitizing EGFR mutation-positive histology.

For glioblastoma: recurrent disease or requires symptom management.

For RCC: disease is relapsed or metastatic, and prescribed as single-agent, in combination with everolimus, or (for advanced papillary RCC including HLRCC-associated RCC only) in combination with erlotinib.

For cervical cancer: disease is persistent, recurrent, or metastatic, and prescribed as single-agent or in combination with paclitaxel/cisplatin (with or without atezolizumab), paclitaxel/carboplatin (with or without atezolizumab), paclitaxel/topotecan, or in combination with pembrolizumab (Keytruda), paclitaxel, and cisplatin/carboplatin for PD-L1–positive disease.

For epithelial ovarian/fallopian tube/primary peritoneal cancer: prescribed as single-agent; or in combination with a platinum agent and chemotherapy followed by single-agent bevacizumab; or for maintenance in combination with olaparib (Lynparza) or niraparib (Zejula) when Lynparza is not tolerated; or for platinum-resistant disease in combination with paclitaxel, liposomal doxorubicin, topotecan, gemcitabine, cyclophosphamide, or specified targeted agents (Ixempra, Elahere, or in combination with cyclophosphamide + pembrolizumab as clinically indicated); or for platinum-sensitive disease in combination with specified platinum regimens or targeted agents as detailed in guidelines.

For HCC: prescribed in combination with atezolizumab (Tecentriq) as first-line systemic therapy for unresectable or metastatic disease, or as subsequent-line systemic therapy if progression on/after systemic therapy.

Biosimilar redirection / step therapy

For requests for Alymsys, Avastin, Avzivi, Jobevne, or Vegzelma: member must use Mvasi or Zirabev unless both are contraindicated or clinically significant adverse effects are experienced, or the request is for treatment in a state with regulations against oncology step therapy (see Appendix E). Prior authorization may be required for Mvasi and Zirabev.

Prescribed regimen must be FDA-approved or recommended by NCCN (prescriber must submit supporting evidence if regimen is off-label).

Dose limits

Dose does not exceed 15 mg/kg IV every 3 weeks or 10 mg/kg IV every 2 weeks (see Appendix F for dose rounding guidelines).
Alternatively, dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

For Illinois HIM requests, the step therapy requirements do not apply per IL HB 5395 effective 1/1/2026.

Approval duration: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less.

Prior Authorization

Ophthalmology formulation restriction

Requests for ophthalmology uses must be for bevacizumab intravitreal solution; IV formulations will not be approved for ophthalmology indications.

Ophthalmology formulation restriction

Documentation Required

Off‑label evidence submission

For off-label uses or doses outside standard limits, the prescriber must submit supporting evidence from practice guidelines or peer‑reviewed literature to support the requested use or dose.

Off-label evidence submission

Billing Rule

Dose rounding guidance

Follow Appendix F vial quantity recommendations for weight‑based dose rounding; Appendix F provides specific vial combinations and weight-based dosing recommendations.

Dose rounding guidance

Prior Authorization

Prescriber specialty requirement

Drug must be prescribed by or in consultation with an oncologist for oncology indications and by or in consultation with an ophthalmologist for ophthalmology indications.

Prescriber specialty requirement

Prior Authorization

Prior authorization and approval duration changes

Prior authorization requirements apply per Health Plan. Approval duration: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less. Step therapy bypass for IL HIM per IL HB 5395 as noted in policy.

Prior authorization and approval duration changes

Billing Rule

Use appropriate HCPCS/Q-code for billed biosimilar

Report the currently appropriate HCPCS/Q-code for the specific bevacizumab biosimilar administered. Current covered HCPCS/Q-codes referenced include Q5107, Q5118, Q5126, Q5129, Q5160, J9035, C9257, and J9999. The policy notes historical additions/removals (example: C9142 was added then removed).

Use appropriate HCPCS/Q-code for billed biosimilar

Documentation Required

Ophthalmology prescriber requirement

For ophthalmology indications, prescriber must be an ophthalmologist as required by the policy.

Ophthalmology prescriber requirement

• FOLFOX: fluorouracil, leucovorin, and oxaliplatin (CRC regimen).

• nAMD: neovascular (wet) age-related macular degeneration (an ophthalmology indication).

• HIM: Health Insurance Marketplace/Managed plan designation (referenced for IL HIM step therapy bypass per IL HB 5395 and approval duration changes).

05.04.22rt_update

RT4 update: added newly FDA‑approved biosimilar Alymsys to policy and generalized language for oncology redirection to preferred agents.

10.24.22annual_review

4Q2022 annual review: added NCCN‑supported indications (ampullary adenocarcinoma, peritoneal mesothelioma, pediatric diffuse high‑grade glioma); reclassified glioma subtypes; removed select prior indications/qualifiers per NCCN; aligned initial approval durations to 6 months; aligned redirection to Mvasi or Zirabev; added HCPCS code C9142 (later removed) and added Vegzelma biosimilar.

01.06.23coding_update

HCPCS code update: removed C9142 and added Q5126 (Alymsys) to the policy coding list.

04.17.23coding_update

HCPCS coding addition: Q5129 (Vegzelma) added to policy coding list.

06.07.23appendix_update

Appendix E (states with regulations against redirection) updated to include Oklahoma.

12.14.23rt_update

RT4 update: added newly FDA‑approved biosimilar Avzivi to the policy and created a separate section for oncology non‑FDA‑approved uses.

06.05.24appendix_update

Appendix E updated to include Mississippi.

11.24.24annual_review

4Q2024 annual review: reorganized FDA‑approved indications for clarity; multiple oncology updates per NCCN (NSCLC, RCC, ovarian, HCC, CRC, cervical cancer) including new qualifiers and regimen clarifications; expanded off‑label oncology uses; ophthalmology updates including allowing choroidal neovascularization for any cause, adding radiation retinopathy and ROP, requiring ophthalmologist prescriber, and removing pediatric age restriction.

05.05.25rt_update

RT4 update: added newly FDA‑approved biosimilar Jobevne to criteria; updated cervical cancer and HCC combination therapy options per NCCN.

05.14.25appendix_update

Appendix E updated language and an exception for Tennessee.

07.30.25annual_review

4Q2025 annual review: added step therapy bypass for Illinois HIM per IL HB 5395; extended initial approval duration for Medicaid and HIM from 6 months to 12 months for maintenance therapy; revised oncology and ophthalmology criteria per NCCN and added additional off‑label uses.

01.06.26coding_update

HCPCS coding addition: Q5160 (Jobevne) added to policy coding list.

03.26.26appendix_updateLatest

Appendix E updated to include Indiana.