Zaltrap (ziv-aflibercept) — Intravenous prior authorization and coverage criteria
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Prior authorization, dosing, and medical necessity criteria for intravenous ziv-aflibercept (Zaltrap) for oncology indications (primarily metastatic colorectal and appendiceal adenocarcinoma) for Moda Health providers and reviewers.
No material clinical or coverage changes in this revision.
Coverage and Medical Necessity Criteria
Initial Therapy
Covered when ALL of the following are met
Universal safety criteria
NCCN recommends universal MMR/MSI testing; consider checkpoint inhibitor for dMMR/MSI-H or ultra-hypermutated POLE/POLD1 tumors (e.g., TMB>50 mut/Mb) when appropriate.
NCCN recommends universal MMR/MSI testing; consider checkpoint inhibitor for dMMR/MSI-H or ultra-hypermutated POLE/POLD1 tumors when appropriate.
Continuation/Renewal Therapy
Renewal criteria — prior authorization may be renewed when ALL of the following are met
Renew every 6 months
Do not approve ziv‑aflibercept when the patient meets any of the following exclusion conditions: recent history of severe hemorrhage; a surgical wound that has not fully healed; or when ziv‑aflibercept would be administered within 4 weeks of major surgery. These universal safety criteria align with the policy's initial-approval requirements and are intended to reduce the risk of bleeding and impaired wound healing.
Additionally, requests should be evaluated for the presence of drug‑related toxicities listed under the renewal criteria. Examples of unacceptable toxicities that would support exclusion or discontinuation include hemorrhage, gastrointestinal perforation, fistula formation, uncontrolled hypertension, impaired wound healing, arterial thromboembolic events, proteinuria ≥2 g/24h, neutropenic complications, reversible posterior leukoencephalopathy syndrome (RPLS), and severe diarrhea/dehydration.
This policy text is intended for non‑Medicare coverage determinations. Where applicable, Medicare rules and guidance take precedence: follow the Medicare Benefit Policy Manual (Pub. 100‑2), Chapter 15, §50, and any applicable National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), or Local Coverage Articles (LCAs). The CMS Medicare coverage database may be searched for NCD/LCD/LCA documents at https://www.cms.gov/medicare-coveragedatabase/search.aspx; compliance with those Medicare documents is required for Medicare members.
Use of ziv‑aflibercept is not medically necessary when the universal safety conditions are not met. Specifically, lack of documentation that the patient does not have a recent severe hemorrhage, has an unhealed surgical wound, or will not receive the drug within 4 weeks of major surgery should support a denial. Likewise, presence of unacceptable drug‑related toxicities (see examples under renewal criteria) renders ongoing therapy not medically necessary.
| Regimen | Dose / Schedule | Indication / Context |
|---|---|---|
| Ziv‑aflibercept (Zaltrap) in combination with FOLFIRI | 4 mg/kg IV every 2 weeks | Metastatic colorectal cancer: used after resistance to or progression following an oxaliplatin‑containing regimen or as specified for unresectable metastases; given in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) |
| Ziv‑aflibercept (Zaltrap) in combination with irinotecan | 4 mg/kg IV every 2 weeks | Metastatic colorectal cancer or appendiceal adenocarcinoma: used as subsequent therapy for progression of advanced/metastatic disease provided the patient has not previously received irinotecan‑based therapy; administered with irinotecan when indicated |
Billing and Code References
| J9400 | Injection, ziv-aflibercept, 1 mg; 1 billable unit = 1 mg |
| 00024-5840 | Zaltrap 100 mg/4 mL solution, single-dose vial (NDC prefix) |
| 00024-5841 | Zaltrap 200 mg/8 mL solution, single-dose vial (NDC prefix) |
| 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 large intestines |
| C18.9 | Malignant neoplasm of colon, unspecified |
| 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 large intestines |
| C18.9 | Malignant neoplasm of colon, unspecified |
Prior Authorization, Documentation, and Provider Requirements
Prior authorization required; initial 6‑month approval
Submit a prior authorization request before initiating ziv‑aflibercept; initial approvals are valid for 6 months and may be renewed every 6 months. Initial approval requires the patient be at least 18 years of age and meet the universal safety criteria and indication‑specific requirements (e.g., metastatic CRC progressed on or resistant to an oxaliplatin‑containing regimen and planned use with FOLFIRI).
- Initial prior authorization validity: 6 months; renew every 6 months.
- Age requirement for initial approval: patient ≥18 years.
- Requests must document universal safety criteria and indication‑specific criteria (see CRC and appendiceal sections).
PA may be required per NQTL/utilization management
Prior authorization may be applied as part of utilization management based on the NQTL assessment — factors considered include indication and drug cost; include a supported covered diagnosis from Appendix 1 when PA is requested.
- NQTL checklist notes cost of drug as a reason to consider PA.
- Include a covered ICD‑10 diagnosis code from Appendix 1 with the request.
Therapy sequencing: use after oxaliplatin‑containing regimens (metastatic CRC)
Use ziv‑aflibercept in metastatic colorectal cancer after disease progression on or resistance to an oxaliplatin‑containing regimen; therapy is expected to be given in combination with FOLFIRI or irinotecan per the indication‑specific language.
- Indication: metastatic CRC resistant to or progressed following an oxaliplatin‑containing regimen (e.g., FOLFOX, CapeOX).
- Administer in combination with FOLFIRI or irinotecan as described.
Step therapy not specified
No formal step therapy requirements are specified in this policy; there are no step‑through mandates described in the document.
- The policy does not define a step therapy pathway for ziv‑aflibercept.
Document metastatic CRC/appendiceal diagnosis and prior oxaliplatin exposure
Provide documentation that supports a diagnosis of metastatic colorectal cancer or appendiceal adenocarcinoma and that the patient has received prior oxaliplatin‑containing therapy where indicated; include prior regimen name(s), timing (e.g., FOLFOX/CapeOX within past 12 months when relevant), and intended combination regimen (FOLFIRI/irinotecan).
- Document histologic diagnosis of metastatic CRC or appendiceal adenocarcinoma.
- Document prior oxaliplatin‑containing regimen and timing (e.g., FOLFOX/CapeOX within past 12 months if applicable).
- Document whether patient has prior irinotecan exposure and planned combination with FOLFIRI or irinotecan.
Submit covered ICD‑10 diagnosis from Appendix 1
When requesting coverage, submit a diagnosis that matches one of the covered ICD‑10 codes listed in Appendix 1 (e.g., C18.0–C18.9, C19, C20, C78.xx, Z85.038).
- Appendix 1 lists the covered ICD‑10 codes to be used on requests.
Denial risk: recent severe hemorrhage, unhealed wound, recent major surgery, or unacceptable toxicity
Therapy may be denied if the patient has recent severe hemorrhage, an unhealed surgical wound, has undergone major surgery within the prior 4 weeks, or is experiencing unacceptable drug‑related toxicities (examples include hemorrhage, GI perforation/fistula, uncontrolled hypertension, impaired wound healing, arterial thromboembolic events, proteinuria ≥2 g/24 h, neutropenia complications, RPLS).
- Do not approve if recent severe hemorrhage or an unhealed surgical wound is present.
- Do not approve if administration would occur within 4 weeks of major surgery.
- Unacceptable toxicities listed under renewal criteria may also lead to denial.
PA considered due to drug cost and utilization management NQTLs
Prior authorization may be considered specifically because of the drug’s cost and as part of utilization management — the NQTL factor checklist identifies cost as a reason to consider PA and lack of PA where appropriate could result in denial.
- NQTL checklist flags 'cost of drug' as a factor to consider for PA.
- Include complete supporting documentation to address utilization management concerns.
Line-of-Therapy Positioning
second-line
Specific prior regimen and timing required
Approved Regimens and Dosing
| Recommended Dosing | Route | Duration / Treatment Until |
|---|---|---|
| 4 mg/kg every 2 weeks | Intravenous (IV) infusion | Continue until disease progression or unacceptable toxicity |
Clinical Definitions and Biomarker Requirements
Drug Background and Indications
Ziv‑aflibercept (Zaltrap) is indicated for use in metastatic colorectal cancer and appendiceal adenocarcinoma in the settings described in this policy. The agent is administered intravenously in combination with irinotecan‑based regimens (commonly FOLFIRI) for patients whose disease is resistant to or has progressed after an oxaliplatin‑containing regimen, or as subsequent therapy for progressive advanced/metastatic disease when prior irinotecan exposure rules permit. Dosing guidance in the policy specifies ziv‑aflibercept 4 mg/kg IV every 2 weeks in combination with FOLFIRI or irinotecan for the covered indications.
The policy also references standard oncology practice considerations relevant to patient selection: treatment is for adults (initial approvals require age ≥18), documentation must support a covered diagnosis (see Appendix 1 ICD‑10 codes), and clinicians should consider biomarker testing (MMR/MSI, POLE/POLD1, TMB) per guideline recommendations because dMMR/MSI‑H or ultra‑hypermutated tumors may be managed with checkpoint inhibitors rather than anti‑VEGF therapy.
Policy Revision History
Policy became effective for coverage and prior authorization of ziv-aflibercept (Zaltrap).
Policy underwent review (last review date recorded).
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