Ciombor KK, Berlin J, Chan E
Clin Cancer Res. 2013 19 (8): 1920-5

PMID: 23444216 · PMCID: PMC3710732 · DOI:10.1158/1078-0432.CCR-12-2911

Aflibercept, an intravenously administered anti-VEGF and antiplacental growth factor (PlGF) agent, has recently been approved by the U.S. Food and Drug Administration in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer who have previously received an oxaliplatin-containing chemotherapy regimen. In the phase III VELOUR trial, aflibercept plus FOLFIRI statistically significantly prolonged both progression-free survival (PFS; median PFS for the aflibercept plus FOLFIRI arm was 6.90 vs. 4.67 months for the placebo-plus-FOLFIRI arm) and overall survival (median overall survival for the aflibercept-plus-FOLFIRI arm was 13.50 vs. 12.06 months for the placebo plus FOLFIRI arm), but grade 3 or 4 adverse events were more common with the addition of aflibercept. However, the addition of aflibercept to 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in the phase II AFFIRM trial of first-line treatment of mCRC failed to improve PFS or response rate. As a decoy VEGF receptor, aflibercept (VEGF-Trap) has binding affinity for VEGF-A, VEGF-B, PlGF-1, and PlGF-2, and this is a mechanism of significant interest. Optimal strategies for incorporating aflibercept into treatment regimens that include other anti-VEGF and cytotoxic chemotherapeutic agents, as well as development of predictive biomarkers for treatment response, have yet to be defined.

MeSH Terms (22)

Antineoplastic Combined Chemotherapy Protocols Camptothecin Clinical Trials, Phase II as Topic Clinical Trials, Phase III as Topic Colorectal Neoplasms Disease-Free Survival Fluorouracil Humans Irinotecan Leucovorin Neoplasm Metastasis Organoplatinum Compounds Oxaliplatin Placenta Growth Factor Pregnancy Proteins Protein Binding Randomized Controlled Trials as Topic Receptors, Vascular Endothelial Growth Factor Recombinant Fusion Proteins Treatment Outcome Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor B

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