ModifiedNeighborhood Health Plan of Rhode IslandPolicy N/A

Zaltrap (ziv‑aflibercept) coverage guideline

Defines accepted indications, continuation rules, exclusions, and billing code for ziv‑aflibercept (Zaltrap) as processed by Evolent for Neighborhood Health Plan of Rhode Island lines of business. Specifies clinical evidence sources required to support use.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyZaltrap (ziv‑aflibercept) coverage guideline

Policy CodePolicy N/A

Change TypeTemplate conversion and administrative updates

Effective Date

Next Review Date

Key ActionEvolent will process all medication requests; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

POLICY UPDATE CHANGES

Converted to new Evolent guideline template in February 2025 replacing prior UM ONC_1226 Zaltrap guideline.

February 2024 update: Updated NCH verbiage to Evolent and updated continuation request verbiage.

1HCPCS J‑code listed

1Lines of Business Applicable

1Excluded Indications (metastatic colorectal cancer)

Coverage Summary

This policy defines accepted indications, continuation rules, exclusions, and the billing code for Zaltrap (ziv‑aflibercept) as processed by Evolent for Neighborhood Health Plan of Rhode Island. Coverage stance is mixed. The scope includes: accepted indications (per FDA labeling, CMS‑approved compendia, NCCN/ASCO guidelines, and peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15), continuation request exemptions when criteria are met (no disease progression, no authorization lapse > 30 days within the last year, and no addition of medications), explicit exclusions (including disease progression on Zaltrap, dosing above the single dose limit of 4 mg/kg, and investigational/off‑label uses lacking sufficient evidence), and the applicable HCPCS billing code J9400 (injection, ziv‑aflibercept; 1 mg).

Colorectal Cancer Position

Policy position for metastatic colorectal cancer:

Zaltrap (ziv‑aflibercept) is not supported by Evolent Policy for metastatic colorectal cancer due to lack of Level 1 evidence showing superiority to bevacizumab (Avastin) or bevacizumab biosimilar‑based regimens and concerns about increased risk of infections and proteinuria

References cited include randomized trial and meta-analysis safety signal

Continuation Therapy Criteria

Continuation Requests Exemption

Continuation requests for a not-approvable medication shall be exempt provided 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 authorizationno lapse > 30 days

Additional medication(s) are not being added to the continuation request

Exclusions and Unproven / Off‑Label Uses

Exclusion Criteria

Use is excluded when any of the following are present:

Disease progression while taking Zaltrap (ziv‑aflibercept)

Dosing exceeds single dose limit of Zaltrap (ziv‑aflibercept)single dose > 4 mg/kg

Investigational use of Zaltrap (ziv‑aflibercept) with an off‑label indication that is not sufficient in evidence or is not generally accepted by the medical community

Sufficient evidence criteria defined separately

Insufficient Evidence — Off‑Label Use

Off‑label uses are considered insufficient when any of the following apply:

Clinical characteristics of the patient and cancer are not adequately represented in the published evidence

The administered chemo/biologic/immune/targeted/other oncologic therapy regimen is not adequately represented in the published evidence

Reported study outcomes do not represent clinically meaningful outcomes (ASCO definitions suggested: HR < 0.80 and OS/PFS benefit ≥ 3 months)

Experimental design is inappropriate to address the investigative question

Non‑randomized clinical trials without a significant number of subjects, case reports, or abstracts without full peer‑reviewed articles are considered inadequate supportive evidence

Denial Risk

Off‑label / investigational use risk

Off‑label indications lacking sufficient evidence or general acceptance may be excluded and not reimbursed.

Provider Actions & Requirements

Prior Authorization

Medication requests processed by Evolent

Evolent is responsible for processing all medication requests; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

J9400

Documentation Required

Evidence support requirement

Use must be supported by FDA labeling, CMS‑approved compendia, NCCN/ASCO guidelines, or peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements.

Denial Risk

Disease progression exclusion

Claims for members with documented disease progression while on Zaltrap are excluded.

J9400

Clinical Evidence

Van Cutsem et al. 2012KEY RCT: Phase III showed addition of aflibercept to FOLFIRI improved survival in previously oxaliplatin‑treated mCRC

Zhang et al. 2016Safety signal: meta‑analysis found increased risk of severe infections with aflibercept

Prescribing information 2023Regulatory/safety details and dosing limits per Zaltrap PI (Sanofi) — single dose limit ≤4 mg/kg cited in policy

Van Cutsem et al., J Clin Oncol. 2012 — Phase III randomized trial reporting that addition of aflibercept to FOLFIRI improved survival in previously oxaliplatin‑treated metastatic colorectal cancer.

Zhang et al., 2016 — Systematic review and meta‑analysis reporting an increased risk of severe infections associated with aflibercept.

Zaltrap prescribing information, Sanofi‑Aventis U.S. LLC, 2023 — official product labeling and prescribing information.

The brief notes there is no Level 1 evidence demonstrating superiority of Zaltrap over bevacizumab (Avastin) or bevacizumab biosimilar‑based regimens for metastatic colorectal cancer and highlights safety concerns including increased risk of infections and proteinuria.

Background

This Evolent clinical guideline defines accepted indications for Zaltrap (ziv‑aflibercept) and requires that use be supported by FDA labeling, CMS‑approved compendia, NCCN and ASCO guidelines, or peer‑reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements. The guideline references key literature including Van Cutsem et al. (J Clin Oncol. 2012) and supportive references, and it explicitly states that there is a lack of Level 1 evidence showing Zaltrap regimens are superior to bevacizumab (Avastin) or bevacizumab biosimilar‑based regimens for metastatic colorectal cancer while calling out safety concerns (increased infections and proteinuria) identified in meta‑analyses.

Sufficient evidence: Evidence supported by CMS‑recognized compendia or acceptable peer‑reviewed literature that adequately represents the patient and cancer characteristics and administered regimen, reports clinically meaningful outcomes (ASCO‑recommended definitions such as HR < 0.80 and OS/PFS benefit ≥ 3 months), and is derived from an appropriate experimental design; non‑randomized trials with substantial subjects may be supportive, whereas case reports and abstracts without full peer‑reviewed articles are inadequate.