00024-5840-XX ZALTRAP 100MG/4ML Solution (SANOFI-AVENTIS U.S.)
00024-5841-XX ZALTRAP 200MG/8ML Solution (SANOFI-AVENTIS U.S.)
Ziv-aflibercept is a recombinant fusion protein which consists of the binding portions of vascular endothelial growth factor (VEGF) from VEGF receptors 1 and 2 fused to the Fc (crystallizable fragment) portion of immunoglobulin G1 (IgG1). VEGF receptor 1 (VEGFR-1) and VEGFR-2 are tyrosine kinases present on the surface of endothelial cells. Ziv-aflibercept acts as a soluble receptor that binds to three VEGF family members: VEGF-A, VEGF-B and placental growth factor (PlGF). VEGF proteins are markedly expressed in most human tumors and if activated by binding to their natural receptors, tumor growth is accelerated through neovascularization and increased vascular permeability. Ziv-aflibercept acts as a decoy by binding to VEGF-A,-B and PlGF and stops their activation, inhibiting tumor growth.
Ziv-aflibercept contains the same drug, aflibercept, as the intravitreal preparation, Eylea®, used in the treatment of macular degeneration. To prevent potential medication errors the FDA required the addition of the prefix “ziv” to the generic name of the intravenous agent, ziv-aflibercept.
Ziv-aflibercept for the treatment of colorectal cancer is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Ziv-aflibercept for the treatment of other conditions/diseases is considered investigational.
Ziv-aflibercept is considered medically appropriate if ALL of the following criteria are met:
Individual is 18 years of age or older
Individual must have no recent history of hemorrhage or hemoptysis (the presence of blood in sputum)
Individual must not have had a surgical procedure within the preceding 28 days or have a surgical wound that has not fully healed;
Treatment of colorectal cancer in combination with irinotecan OR FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen for ANY ONE of the following:
Individual has metastatic disease that is resistant to or has progressed following an oxaliplatin-containing regimen (e.g., FOLFOX, CapeOX)
Used as primary treatment for individuals with unresectable metachronous metastases and has received previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
Used as subsequent therapy for progression of unresectable advanced or metastatic disease in an individual who has not previously received irinotecan-based therapy
Ziv-aflibercept is considered medically appropriate for renewal if ALL of the following criteria are met:
Individual continues to meet initial approval criteria
Tumor response with stabilization of disease or decrease in size or spread of tumor
Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: hemorrhage; gastrointestinal perforation; fistula formation; hypertension; wound healing complications; arterial thromboembolic events; proteinuria; neutropenic complications; reversible posterior leukoencephalopathy syndrome (RPLS); severe diarrhea/dehydration; etc
DOSAGE & ADMINISTRATION
4 mg/ kg as an intravenous (IV) infusion over 1 hour every two weeks, until disease progression or unacceptable toxicity.
LENGTH OF AUTHORIZATION
Coverage is provided for six months and may be renewed.
Refer to DOSAGE LIMITS below
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
Lexi-Comp Online. (2019, February). AHFS DI. Ziv-aflibercept. Retrieved February 12, 2020 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2019, December). Ziv-aflibercept. Retrieved February 12, 2020 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2020). NCCN Drugs & Biologics Compendium®. Ziv-aflibercept. Retrieved February 12, 2020 from the National Comprehensive Cancer Network.
U. S. Food and Drug Administration. (2019, November). Center for Drug Evaluation and Research. Zaltrap® (ziv-aflibercept). Retrieved February 12, 2020 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125418s039lbl.pdf.
ORIGINAL EFFECTIVE DATE: 8/13/2012
MOST RECENT REVIEW DATE: 6/30/2020
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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Maximum billable units per dose and over time by indication as a Medical Benefit 1 billing unit = 1 mg