title: Targeting multiple angiogenic pathways simultaneously: experience with nintedanib in non-small-cell lung cancer.
abstract: Angiogenesis plays a major role in the growth and progression of non-small-cell lung cancer (NSCLC), and there is increasing interest in the development of therapies that block this particular aspect of tumorigenesis. Bevacizumab was the first US FDA-approved inhibitor of angiogenesis after demonstrating improved progression-free survival and overall survival in combination with chemotherapy in treating NSCLC. However, the benefit of bevacizumab is only modest and transient as the tumors inevitably develop resistance to this particular treatment. Therefore, new therapies are being developed that attempt to inhibit angiogenesis through several different pathways. One promising new drug, nintedanib, is an oral triple angiokinase inhibitor that acts by blocking not only VEGFR, but also FGFR and PDGFR, which are involved in the development of resistance to bevacizumab. This article discusses the rationale for this approach and summarizes the clinical trial data on nintedanib, including the two most recent Phase III trials.
authors.affiliation: IU School of Medicine, 535 Barnhill Drive, RT 473 Indianapolis, IN 46202, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Durm
authors.forename: Nasser
authors.initials: N
authors.lastname: Hanna
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D000068258:Bevacizumab; C530716:nintedanib
keywords: FGFR; PDGFR; VEGFR; angiogenesis; nintedanib