Nintedanib in non-small cell lung cancer: from preclinical to approval
Caglevic C(1), Grassi M(2), Raez L(3), Listi A(4), Giallombardo M(5), Bustamante E(6), Gil-Bazo I(7), Rolfo C(8).
(1) Oncology Department, Arturo Lopez Perez Cancer Foundation, Santiago, Chile.
(2) Phase I - Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Edegem, Belgium.
(3) Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, FL, USA.
(4) Department of Surgical, Oncological and Stomatological Sciences, Section of Medical Oncology, University of Palermo, Italy.
(5) 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.
(6) Molecular Biology Unit, Arturo Lopez Perez Cancer Foundation, Santiago, Chile.
(7) Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
(8) Head of Phase I - Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital and Antwerp University, Wilrijkstraat 10, 2650 Edegem, Belgium.
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.
CITATION Ther Adv Respir Dis. 2015 Apr 7. pii: 1753465815579608.