title: Nintedanib in non-small cell lung cancer: from preclinical to approval.
abstract: Angiogenesis is a driving force of a tumor's development. Targeting this process is an attractive option, as this is a feature shared by most of the solid tumors. A lot of antiangiogenic drugs have been developed following this path, including bevacizumab, sorafenib, sunitinib, vandetanib, ramucirumab, motesanib and many others. The latest drug of this class to be approved for patients with non-small cell lung cancer (NSCLC) was nintedanib, a triple angiokinase inhibitor. This molecule targets vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways, avoiding the tumor's switch to normal escape mechanisms. The pharmacokinetic, pharmacodynamic and toxicity profiles of nintedanib have been tested in several studies. These trials revealed it to be very interesting, as this agent did not lead to the classical adverse events of other tyrosine kinase inhibitors. A phase III clinical trial that recently concluded provided us with relevant information in patients with NSCLC of adenocarcinoma histology. Here we present a short overview of the tumor angiogenesis pathways and antiangiogenic drugs. In particular, we will focus on nintedanib, from the preclinical studies to the latest phase III clinical trial that allowed this new agent to be approved by the European Medicines Agency as a second-line treatment option in association with docetaxel for NSCLC patients with adenocarcinoma histology.
authors: Oncology Department, Arturo Lopez Perez Cancer Foundation, Santiago, Chile.
authors: Christian
authors: C
authors: Caglevic
authors: Phase I - Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Edegem, Belgium.
authors: Massimiliano
authors: M
authors: Grassi
authors: Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, FL, USA.
authors: Luis
authors: L
authors: Raez
authors: Department of Surgical, Oncological and Stomatological Sciences, Section of Medical Oncology, University of Palermo, Italy.
authors: Angela
authors: A
authors: Listi
authors: Phase I - Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Edegem, Belgium Department of Biopathology and Medical Biotechnology and Forensic Section of Biology and Genetics, University of Palermo, Italy Tumor Immunotherapy Laboratory, Oncology Department, Antwerp University Hospital, Edegem, Belgium.
authors: Marco
authors: M
authors: Giallombardo
authors: Molecular Biology Unit, Arturo Lopez Perez Cancer Foundation, Santiago, Chile.
authors: Eva
authors: E
authors: Bustamante
authors: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
authors: Ignacio
authors: I
authors: Gil-Bazo
authors: Head of Phase I - Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital and Antwerp University, Wilrijkstraat 10, 2650 Edegem, Belgium christian.rolfo@uza.be.
authors: Christian
authors: C
authors: Rolfo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; C530716:nintedanib
keywords: BIBF1120; NSCLC; antiangiogenic drugs; nintedanib; non-small cell lung cancer; tyrosine kinase inhibitor