Abstract
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
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Camptothecin / administration & dosage
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Camptothecin / analogs & derivatives
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Clinical Trials, Phase II as Topic
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Clinical Trials, Phase III as Topic
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Disease-Free Survival
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Fluorouracil / administration & dosage
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Humans
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Irinotecan
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Leucovorin / administration & dosage
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Neoplasm Metastasis
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Organoplatinum Compounds / administration & dosage
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Oxaliplatin
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Placenta Growth Factor
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Pregnancy Proteins / metabolism
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Protein Binding
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Randomized Controlled Trials as Topic
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Receptors, Vascular Endothelial Growth Factor / administration & dosage
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Receptors, Vascular Endothelial Growth Factor / therapeutic use*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / therapeutic use*
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Treatment Outcome
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor B / metabolism
Substances
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Organoplatinum Compounds
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PGF protein, human
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Pregnancy Proteins
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Recombinant Fusion Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor B
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Oxaliplatin
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Placenta Growth Factor
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aflibercept
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Irinotecan
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Receptors, Vascular Endothelial Growth Factor
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Leucovorin
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Fluorouracil
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Camptothecin