title: Targeting the VEGF pathway: antiangiogenic strategies in the treatment of non-small cell lung cancer.
abstract: The management of advanced non-small cell lung cancer (NSCLC) has evolved considerably in recent years, due to a progressive understanding of tumour biology and the identification of promising molecular targets. Several agents have been developed so far inhibiting vascular endothelial growth factor (VEGF) - a key protein in tumour neoangiogenesis, growth and dissemination - or its receptor signalling system. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab - a humanised anti-VEGF monoclonal antibody - over chemotherapy (CT) alone led the U.S. Food and Drug Administration (FDA) to approve the novel combination for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. In a randomised phase III trial presented at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival (PFS) compared to the standard arm. Based on these data, the European Medicines Agency (EMEA) has granted marketing authorisation for bevacizumab in addition to any platinum-based CT for first-line treatment of advanced NSCLC other than predominantly squamous histology. Aim of this report is to provide an overview on bevacizumab in NSCLC, with special emphasis on clinical results presented at ASCO last meeting. Multitargeted tyrosine kinase inhibitors (TKIs), sharing a focus on both the angiogenesis process and additional cell-surface receptors, and VEGF Trap, a novel fusion protein with markedly higher affinity for VEGF than bevacizumab, will be briefly discussed as well.
authors.affiliation: Department of Medical Oncology, University Hospital of Udine, Piazzale S.M. della Misericordia 15, 33100 Udine, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Aita
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.forename: Carlotta
authors.initials: C
authors.lastname: Defferrari
authors.forename: Annalisa
authors.initials: A
authors.lastname: Brianti
authors.forename: Maria Giovanna Dal
authors.initials: MG
authors.lastname: Bello
authors.forename: Alessandro
authors.initials: A
authors.lastname: Follador
authors.forename: Graziella
authors.initials: G
authors.lastname: Sinaccio
authors.forename: Paolo
authors.initials: P
authors.lastname: Pronzato
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab