Ziv-aflibercept acts as a soluble receptor for VEGF and placental growth factor (PLGF). It is designed to function as a VEGF "trap" to prevent activation of VEGF receptors and inhibit angiogenesis. In animal models, ziv-aflibercept inhibited the proliferation of endothelial cells and the growth of new blood vessels.

Ziv-aflibercept is indicated for use in combination with 5-FU, leucovorin, and irinotecan (the FOLFIRI regimen) for patients with mCRC that is resistant to, or has progressed following, an oxaliplatin-containing regimen.

Boxed warnings associated with the use of ziv-aflibercept are similar to those for bevacizumab. The prescribing information for ziv-aflibercept has warnings related to the potential for hemorrhage, gastrointestinal perforation, and compromised wound healing.