CurrentCareSourcePolicy N/A

Zaltrap (ziv-aflibercept) for colorectal and appendiceal cancer — Prior authorization and coverage criteria

Policy governs prior authorization and medical necessity criteria for intravenous Zaltrap (ziv-aflibercept) for treatment of colon, rectal, and appendiceal adenocarcinoma in the metastatic/unresectable setting for CareSource members and prescribers.

Policy Summary

PayerCareSource

PolicyZaltrap (ziv-aflibercept) for colorectal and appendiceal cancer — Prior authorization and coverage criteria

Policy CodePolicy N/A

Change TypeMaterial clinical revisions

Effective Date

Next Review Date

Key ActionObtain prior authorization and document prior treatment with FOLFOX or CapeOX; approvals are recommended for 1 year when criteria and dosing are met.

SourceLink

POLICY UPDATE CHANGES

Appendiceal Adenocarcinoma was added to the condition of approval.

Revised criterion from 'oxaliplatin- or fluoropyrimidine-containing regimen' to specified prior treatment with FOLFOX or CapeOX; note updated to include regimen components.

Removed descriptor 'or capecitabine' from requirement that Zaltrap be used in combination with 5-FU and/or irinotecan.

1 yeartypical approval duration

4 mg/kgmax dose per infusion

q2wdosing frequency

10/30/2024selected revision date

Policy Summary

PayerCareSource

PolicyZaltrap (ziv-aflibercept) for colorectal and appendiceal cancer — Prior authorization and coverage criteria

Policy CodePolicy N/A

Change TypeMaterial clinical revisions

Effective Date

Next Review Date

Key ActionObtain prior authorization and document prior treatment with FOLFOX or CapeOX; approvals are recommended for 1 year when criteria and dosing are met.

SourceLink

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Recommended Authorization Criteria

FDA-Approved Indication and Authorization Criteria

Covered when ALL of the following are met:

Age: Patient is ≥ 18 years of age.>=18 years

Indication: Diagnosis is colon cancer, rectal cancer, or appendiceal adenocarcinoma (metastatic/unresectable).

Clinical scenario

Initial therapy path: Patient has unresectable metachronous metastases AND disease is proficient mismatch repair/microsatellite-stable (pMMR/MSS) AND medication is used for initial therapy AND patient has been previously treated with FOLFOX or CapeOX (within prior therapy history).
FOLFOX includes 5-FU, leucovorin, and oxaliplatin; CapeOX includes capecitabine and oxaliplatin.
Subsequent therapy path: Patient has advanced or metastatic disease AND (disease is pMMR/MSS OR patient is ineligible for or has progressed on checkpoint inhibitor therapy for dMMR/MSI-H or POLE/POLD mutation positive disease) AND patient has NOT previously been treated with irinotecan or FOLFIRI AND Zaltrap will be used in combination with 5-FU and/or irinotecan AND medication is used for subsequent therapy.
Examples of checkpoint inhibitors include pembrolizumab and nivolumab.

Combination therapy: Zaltrap will be used in combination with 5-fluorouracil (5-FU) and/or irinotecan.

If used as subsequent therapy, patient must not have prior irinotecan/FOLFIRI exposure per criteria.

Prescriber: Medication is prescribed by or in consultation with an oncologist.

Coverage of Zaltrap is recommended only when the member meets the specific authorization criteria listed in this policy. Requests that do not meet these Recommended Authorization Criteria are not recommended for approval and may be denied. The criteria in this policy will be updated as new published evidence becomes available to ensure alignment with current clinical standards and regulatory guidance.

Regimen	Dose / Frequency	Required combination	Coverage status
Zaltrap (ziv-aflibercept) IV
Up to 4 mg/kg per infusion; no more frequently than once every 2 weeks
Must be used in combination with 5-fluorouracil (5-FU) and/or irinotecan (e.g., FOLFIRI)
Covered with criteria

Line of Therapy Criteria

first-line

Initial therapy line: Unresectable metachronous metastases after prior FOLFOX or CapeOX (within prior therapy history), disease is pMMR/MSS, medication used for initial therapy and administered in combination with irinotecan or as part of FOLFIRI.

FOLFOX = 5-FU + leucovorin + oxaliplatin; CapeOX = capecitabine + oxaliplatin.

second-line

Subsequent therapy line: Used as subsequent therapy after first progression of advanced or metastatic disease (pMMR/MSS) OR when patient is ineligible for or has progressed on checkpoint inhibitor therapy for dMMR/MSI-H or POLE/POLD mutation positive disease; patient has not previously been treated with irinotecan or FOLFIRI; Zaltrap will be used in combination with 5-FU and/or irinotecan.

Examples of checkpoint inhibitors include pembrolizumab and nivolumab.

Biomarker and Molecular Testing Requirements

Biomarker requirements and role in eligibility

Required biomarker testingDocumentation of dMMR/MSI-H or POLE/POLD status is used to determine eligibility for checkpoint inhibitor therapy; patients who are ineligible for or have progressed on checkpoint inhibitors for dMMR/MSI-H or POLE/POLD mutation–positive disease may qualify for subsequent‑therapy Zaltrap per criteria.

Negative biomarker requirement for initial pathDisease must be proficient mismatch repair/microsatellite‑stable (pMMR/MSS) for the initial‑therapy pathway.

Role of biomarkers in subsequent therapyFor subsequent‑therapy path, either disease is pMMR/MSS OR the patient is ineligible for or progressed on checkpoint inhibitors for dMMR/MSI‑H or POLE/POLD mutation‑positive disease.

Checkpoint inhibitor examplesExamples of checkpoint inhibitors cited in the policy include pembrolizumab (Keytruda) and nivolumab (Opdivo).

Impact on prior‑therapy requirementsIf patient progressed on or is ineligible for checkpoint inhibitor therapy for dMMR/MSI‑H or POLE/POLD mutation‑positive disease, patient must not have prior irinotecan/FOLFIRI exposure to be eligible for Zaltrap in subsequent therapy.

Approved Regimens and Dosing

Dosing / Frequency	Combination requirement	Notes
Up to 4 mg/kg per infusion; no more frequently than once every 2 weeks
Zaltrap must be administered in combination with 5-fluorouracil (5-FU) and/or irinotecan (e.g., FOLFIRI)
Coverage requires clinical criteria to be met (age ≥18, indication: colon, rectal, or appendiceal adenocarcinoma metastatic/unresectable, and line-of-therapy requirements per policy). Prior irinotecan/FOLFIRI exposure restrictions apply for subsequent-therapy scenarios.

Prescriber Requirements, Prior Authorization, and Denial Triggers

Prior Authorization

Prior authorization required; standard 1‑year approval

Prior authorization is recommended for medical benefit coverage of Zaltrap. Approvals should be issued for 1 year when the patient meets the policy Criteria and Dosing; extended approvals are allowed if the patient continues to meet Criteria and Dosing.

Step Therapy

Prior regimen: prior FOLFOX or CapeOX required

For the initial‑therapy pathway, the policy requires prior treatment with FOLFOX or CapeOX (oxaliplatin‑containing regimens) before authorizing Zaltrap for unresectable metachronous metastases.

Note: FOLFOX includes 5‑fluorouracil (5‑FU), leucovorin, and oxaliplatin; CapeOX includes capecitabine and oxaliplatin.

Regimen Definitions

Definitions: FOLFOX and CapeOX

FOLFOX componentsFOLFOX consists of 5‑fluorouracil (5‑FU), leucovorin, and oxaliplatin.

CapeOX componentsCapeOX consists of capecitabine and oxaliplatin.

Context of usePolicy requires prior treatment with FOLFOX or CapeOX in the initial‑therapy pathway for unresectable metachronous metastases.

Related regimen noteFOLFOX/CapeOX are referenced as oxaliplatin‑containing regimens in the prior‑therapy requirement.

Background and Clinical Context

Zaltrap (ziv‑aflibercept) is an intravenously administered VEGF‑trap biologic indicated for use in combination with fluoropyrimidine and irinotecan‑containing regimens for treatment of metastatic or unresectable colorectal and appendiceal adenocarcinoma. Per the dosing guidance in this policy, Zaltrap is given IV at a maximum of 4 mg/kg no more frequently than every 2 weeks and is intended to be used in combination with 5‑fluorouracil (and/or irinotecan such as in FOLFIRI) when the clinical criteria for use are met.

Document Revision History

2024-10-30criteria_revisionLatest

Revised prior therapy requirement: criterion changed from 'oxaliplatin- or fluoropyrimidine-containing regimen' to explicitly require prior treatment with FOLFOX or CapeOX and updated note to list regimen components.

2024-10-16language_clarification

Removed the descriptor 'or capecitabine' from the requirement that Zaltrap be used in combination with 5‑fluorouracil (5‑FU) and/or irinotecan.

2023-10-11indication_addition