CurrentEmblemHealthPolicy N/A

Zaltrap (ziv-aflibercept) coverage

Defines accepted indications, exclusions, and authorization requirements for Zaltrap (ziv-aflibercept) for EmblemHealth (managed by Evolent) across applicable lines of business. Affects network ordering providers submitting medication requests to Evolent.

Policy Summary

PayerEmblemHealth

PolicyZaltrap (ziv-aflibercept) coverage

Policy CodePolicy N/A

Change TypeNo material changes

Effective Date

Next Review Date

Key ActionSubmit medication requests for Zaltrap through Evolent and include supporting documentation per FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

J9400HCPCS code

4 mg/kgDose limit

Not supportedmCRC stance

Commercial/MA/Medicaid/CHIPLines of business

Coverage criteria and exclusions

Coverage Criteria and Exclusions

Policy Summary

PayerEmblemHealth

PolicyZaltrap (ziv-aflibercept) coverage

Policy CodePolicy N/A

Change TypeNo material changes

Effective Date

Next Review Date

SourceLink

On This Page

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General requirements: Use must be supported by FDA approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or acceptable peer-reviewed literature meeting CMS criteria.

References and prescribing information cited in policy.

Continuation request exemption: Continuation requests are exempt from this policy if ALL of the following are met: no disease progression on the medication; the medication was used within the last year without a lapse greater than 30 days of an active authorization; and no additional medications are being added to the continuation request.

Continuation rules per prior authorization section.

Exclusions: Requests are excluded if any of the following apply: disease progression while taking Zaltrap (ziv-aflibercept); dosing exceeds the single-dose limit of Zaltrap 4 mg/kg; investigational or off-label use that lacks sufficient evidence as defined by policy (not supported by CMS-recognized compendia or acceptable peer-reviewed literature).

See Exclusion Criteria for evidence definitions and acceptable study types.

Requests are excluded when any of the following apply: disease progression while taking Zaltrap (ziv‑aflibercept); dosing that exceeds the single‑dose limit of 4 mg/kg; or use for investigational or off‑label indications that lack sufficient supporting evidence as defined by the policy (for example, not supported by CMS‑recognized compendia or acceptable peer‑reviewed literature, inadequate representation of the patient population or regimen in published evidence, or reliance on uncontrolled case reports or abstracts without full peer‑reviewed publication).

Zaltrap (ziv‑aflibercept) is not supported by Evolent Policy for metastatic colorectal cancer. This position is based on the lack of Level‑1 evidence showing superiority of aflibercept‑containing regimens over bevacizumab (Avastin)‑based regimens and on safety signals identified in meta‑analyses (including increased risk of infections and proteinuria). Requests for Zaltrap for metastatic colorectal cancer are therefore not approvable as routine coverage under this policy and may be denied.

Prior authorization and documentation requirements

Prior Authorization

Prior Authorization Required

Prior authorization and continuation requests for Zaltrap (ziv‑aflibercept) must be processed through Evolent. Medications not authorized by Evolent may be deemed not approvable and therefore not reimbursable. Continuation requests are exempt from this Evolent policy only when ALL of the following are met: the member has not experienced disease progression on the requested medication; the requested medication was used within the last year without a lapse of more than 30 days of having an active authorization; and no additional medication(s) are being added to the continuation request.

All medication requests must be submitted to Evolent for prior authorization.
Continuation requests are allowed if there has been no disease progression, use within the past year with ≤30‑day lapse, and no new agents are added.

Documentation Required

Supporting Documentation Required

Support for use of Zaltrap must include one or more of the following: FDA approved product labeling, CMS‑recognized compendia (e.g., AHFS, Clinical Pharmacology, Micromedex), NCCN or ASCO clinical guidelines, or acceptable peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 standards. Peer‑reviewed evidence should adequately represent the patient population, regimen, and clinically meaningful outcomes (ASCO definitions such as HR < 0.80 or ≥3‑month OS/PFS benefit where applicable). Case reports and meeting abstracts without full peer‑reviewed articles do not generally provide sufficient evidence.

Acceptable sources: FDA labeling; CMS‑recognized compendia (AHFS, Clinical Pharmacology, Micromedex); NCCN/ASCO guidelines; peer‑reviewed literature meeting CMS standards.
Insufficient: isolated case reports, abstracts without full peer‑reviewed articles.

Note

Preferred Alternatives / Evidence Preference

Evolent prefers alternative agents/regimens per Evolent Pathways and does not support Zaltrap for metastatic colorectal cancer due to lack of Level‑1 evidence showing superior outcomes versus bevacizumab (or biosimilars)‑based regimens and because meta‑analyses have shown increased risk of infections and proteinuria with aflibercept. Providers should consider recommended alternatives listed in Evolent Pathways when applicable.

Zaltrap is not supported by Evolent for metastatic colorectal cancer — see Evolent Pathways for alternative regimens.
Preference is for bevacizumab‑based regimens (including biosimilars) where clinically appropriate.

Line of therapy criteria

Second-line

Line of therapy notes: Although a phase III randomized trial demonstrated improved survival with aflibercept plus FOLFIRI in previously treated metastatic colorectal cancer, Evolent does not support Zaltrap for metastatic colorectal cancer due to lack of Level 1 evidence of superiority to bevacizumab-based regimens and safety concerns (increased risk of infections and proteinuria) reported in meta-analyses.

See J Clin Oncol 2012 and meta-analysis 2016 references.

Regimen	Indication	Policy stance
Ziv-aflibercept (Zaltrap) plus FOLFIRI (fluorouracil, leucovorin, irinotecan)	Metastatic colorectal cancer (previously treated)	Not supported — alternatives preferred (e.g., bevacizumab-based regimens per Evolent pathways)

Definitions and investigational status

Investigational / insufficient evidence

DefinitionInvestigational or off-label use not supported by CMS-recognized compendia or acceptable peer-reviewed literature is excluded.

Evidence standardsAcceptable evidence must adequately represent patient and cancer characteristics, regimens, and report clinically meaningful outcomes (e.g., HR <0.80 or ≥3 months OS/PFS benefit as per ASCO guidance).

Unacceptable evidenceCase reports and meeting abstracts without full peer-reviewed publication generally do not provide adequate supportive evidence.

Policy consequenceUses deemed investigational/insufficiently evidenced are excluded and may be denied for coverage consideration.

Background and clinical context

Ziv‑aflibercept (Zaltrap) is an anti‑angiogenic fusion protein evaluated as part of combination chemotherapy regimens for metastatic colorectal cancer. A randomized phase III trial (Van Cutsem et al.) demonstrated a survival benefit when aflibercept was added to FOLFIRI in previously treated patients; however, the policy notes that available evidence does not establish superiority over bevacizumab‑based regimens and that meta‑analyses report higher rates of certain adverse events (for example, infections and proteinuria). Use of Zaltrap should align with FDA labeling and recognized compendia and be considered in the context of these efficacy and safety findings.

OpenPayer