Ziv-aflibercept (Zaltrap)

Section: Injections
Effective Date: August 01, 2019
Revised Date: July 23, 2019


Ziv-aflibercept (Zaltrap), formerly known as aflibercept, VEGF Trap, is a recombinant fusion protein, which acts as a soluble receptor that binds to vascular endothelial growth factor-A (VEGF-A), VEGF-B and placental growth factor (PIGF). Ziv-aflibercept (Ziltrap) is designed to act as a VEGF trap to prevent activation of VEGF receptors and thus inhibit angiogenesis. Inhibition of these factors can result in decreased neo-vascularization and decreased vascular permeability.


Coverage is subject to the specific terms of the member's benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Ziv-aflibercept (Ziltrap) may be considered medically necessary for the treatment of ANY of the following conditions:

Food and Drug Administration (FDA) Indication

Colorectal Cancer

  • Treatment for metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen, in combinations with FOLFIRI (5-fluorouracil, leucovorin, and irinotecan); or

National Comprehensive Cancer Network (NCCN) Indications

Colon or Rectal Cancer  Adenocarcinoma

  • Primary treatment for individuals with unresectable metachronous metastases and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months in combination with:
    • Irinotecan; or
    • FOLFIRI regimen; or
  • Subsequent therapy after first progression of unresectable advanced or metastatic disease in combination with irinotecan or FOLFIRI regimen not previously treated with irinotecan-based regimens.

Ziv-aflibercept (Ziltrap) is considered experimental/investigational for all other indications and therefore non-covered. Scientific evidence does not support its use for any other indications.

Procedure Codes


NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Diagnosis Codes

Covered Diagnosis Codes for Procedure Code J9400:

C17.0 C17.1 C17.2 C17.8 C17.9 C18.0 C18.1
C18.2 C18.3 C18.4 C18.5 C18.6 C18.7 C18.8
C18.9 C19 C20 C21.8 C78.6 C78.7 C78.00
C78.01 C78.02 Z85.038