CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Zaltrap (ziv-aflibercept) — coverage criteria

Defines accepted indications, exclusions, and coding for ziv-aflibercept (Zaltrap) requests processed by Evolent on behalf of the payer; applies to providers submitting medication requests for covered lines of business.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyZaltrap (ziv-aflibercept) — coverage criteria

Policy CodePolicy N/A

Change TypeTemplate conversion / replacement

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization supported by FDA labeling, CMS compendia, NCCN/ASCO guidance, or acceptable peer‑reviewed literature.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and this guideline replaces UM ONC_1226 Zaltrap (ziv-aflibercept).

J9400HCPCS code

Commercial/Medicaid/ExchangeLines of business

4 mg/kgSingle dose max

Not supportedmCRC stance

Coverage, Limits, and Exclusions

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Coverage and Exclusion Rules

Coverage and exclusion rules as stated by Evolent:

General evidence requirement: Use must be supported by FDA labeling, CMS-approved compendia, NCCN or ASCO clinical guidelines, or acceptable peer-reviewed literature per CMS Medicare Benefit Policy Manual Chapter 15.

Referenced in Purpose and References

Colorectal cancer stance: Zaltrap (ziv-aflibercept) is not supported for metastatic colorectal cancer due to lack of Level 1 evidence of superiority versus bevacizumab-based regimens and meta-analyses showing increased risks (infections, proteinuria).

Providers should use alternative Evolent-recommended regimens (see Evolent Pathways)

Continuation authorization criteria: Continuation allowed if: the member has not experienced disease progression on the medication AND the requested medication was used within the last year without a lapse of more than 30 days of active authorization AND no additional medications are being added to the continuation request.

Applies to continuation requests for a not-approvable medication

Exclusion criteria (any triggers exclusion): Any of the following will exclude approval: disease progression while taking Zaltrap; dosing that exceeds the single dose limit of 4 mg/kg; investigational or off-label use lacking sufficient evidence as defined by CMS-recognized compendia or acceptable peer-reviewed literature.

See policy for definition of sufficient evidence (study design, population, clinically meaningful outcomes)

Exclusions for Zaltrap (ziv‑aflibercept) requests include: disease progression while receiving Zaltrap; any single dose that exceeds 4 mg/kg; and investigational or off‑label indications that lack sufficient evidence as defined by CMS‑recognized compendia or acceptable peer‑reviewed literature. The policy defines sufficient evidence in terms of adequate representation of the patient and regimen in published studies, clinically meaningful outcomes (for example ASCO‑recommended thresholds such as hazard ratio <0.80 or OS/PFS benefit ≥3 months), appropriate study design, and preference for randomized or sizeable non‑randomized trials over case reports or abstracts without full articles.

Use of Zaltrap (ziv‑aflibercept) for metastatic colorectal cancer (mCRC) is not supported by this policy. This position reflects the lack of Level‑1 evidence showing superiority of Zaltrap‑containing regimens versus bevacizumab (Avastin) or bevacizumab biosimilar‑based regimens, and pooled analyses indicating increased risks (for example, infections and proteinuria). Providers should refer to Evolent‑recommended alternative regimens (see Evolent Pathways).

Regimen	Coverage status	Notes
Zaltrap (ziv-aflibercept)–containing regimens for metastatic colorectal cancer
Bevacizumab (Avastin)–based regimens or bevacizumab biosimilars for metastatic colorectal cancer
Evolent-recommended alternative regimens for mCRC (see Evolent Pathways)

Prior Authorization, Documentation, and Denial Triggers

Prior Authorization

Prior Authorization Required

Prior authorization and drug coding — All requests for Zaltrap (ziv‑aflibercept) are processed by Evolent. Requests must be supported by FDA‑approved product labeling, CMS‑recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer‑reviewed literature meeting CMS compendia-match criteria. Use HCPCS code J9400 (Injection, ziv‑aflibercept, 1 mg) for billing.

Evolent processes all medication requests; authorizations not issued by Evolent may be deemed not approvable and not reimbursable.
Required support: FDA labeling; CMS‑recognized compendia; NCCN/ASCO guidelines; acceptable peer‑reviewed literature meeting CMS criteria.

Denial Risk

mCRC Not Supported — Denial Risk

Zaltrap (ziv‑aflibercept) use for metastatic colorectal cancer (mCRC) is not supported by Evolent policy. The position is based on lack of Level 1 evidence showing superior outcomes versus bevacizumab‑based regimens and signals for increased risk of infections and proteinuria.

Zaltrap for mCRC is an explicit non‑supported indication and is generally not approvable.
Refer to alternative agents/regimens recommended by Evolent (see Evolent Pathways) such as bevacizumab/bevacizumab biosimilars‑based regimens.

Documentation Required

Continuation Request Requirements

Continuation request requirements — Continuation (re‑authorization) requests for medications that would otherwise be non‑approvable are eligible for exemption from denial only when all conditions below are met.

Member has not experienced disease progression while receiving the requested medication.
Requested medication was used within the last 12 months without a gap of >30 days from an active authorization.
No additional medication(s) are being added to the continuation request.

Denial Risk

Exclusion Criteria / Denial Triggers

Exclusion conditions that may trigger denial — the following conditions are exclusionary and may lead to denial of coverage for Zaltrap.

Documented disease progression while taking Zaltrap (ziv‑aflibercept).
Dosing that exceeds the single‑dose limit of 4 mg/kg.
Investigational use or off‑label indications lacking sufficient evidence or not generally accepted by the medical community. Insufficient evidence includes lack of representation of patient/cancer characteristics, inadequate representation of the administered regimen, absence of clinically meaningful outcomes (per ASCO definitions, e.g., HR <0.80 and recommended OS/PFS benefit thresholds), inappropriate study design, reliance on uncontrolled case reports or meeting abstracts without full peer‑reviewed publication.

Step Therapy

Preferred Alternatives for mCRC

Preferred alternatives for mCRC — Evolent recommends alternative agents/regimens for metastatic colorectal cancer; Zaltrap is not recommended. Providers should follow Evolent Pathways and consider bevacizumab (Avastin) or bevacizumab biosimilar‑based regimens per current guidelines and compendia.

Zaltrap is not a preferred option for mCRC; use recommended alternatives listed in Evolent Pathways.
When pursuing an alternative regimen, ensure documentation aligns with guideline or compendium support.

Evidence Standards and Definitions

Sufficient evidence for off-label use — acceptable evidence sources

Acceptable evidence sourcesCMS‑recognized compendia or acceptable peer‑reviewed literature meeting CMS standards (e.g., Medicare Benefit Policy Manual Chapter 15)

Clinical representativenessEvidence must adequately represent the clinical characteristics of the patient and the cancer

Regimen representationPublished evidence should adequately represent the administered chemotherapy/biologic/targeted/other oncologic regimen

Clinically meaningful outcomesReported study outcomes should be clinically meaningful (ASCO guidance e.g., HR <0.80 or OS/PFS benefit ≥ 3 months)

Study design standardsAppropriate experimental design is required; nonrandomized trials with substantial subjects may be supportive, while case reports and abstracts without full articles are insufficient

OpenPayer

Zaltrap (ziv-aflibercept) — coverage criteria

Coverage, Limits, and Exclusions

Drug Codes and Dosing Limits

Prior Authorization, Documentation, and Denial Triggers

Evidence Standards and Definitions

Drug Background

Policy Changes and History