title: Aflibercept.
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.
authors: Division of Hematology/Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA.
authors: Kristen K
authors: KK
authors: Ciombor
authors: Jordan
authors: J
authors: Berlin
authors: Emily
authors: E
authors: Chan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D011485:Protein Binding; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042561:Vascular Endothelial Growth Factor B / Q000378:metabolism
chemical_list: D009944:Organoplatinum Compounds; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D000077150:Oxaliplatin; D000072483:Placenta Growth Factor; C533178:aflibercept; D000077146:Irinotecan; D040262:Receptors, Vascular Endothelial Growth Factor; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin