title: Focus on Nintedanib in NSCLC and Other Tumors.
abstract: Nintedanib is a new triple angiokinase inhibitor that potently blocks the proangiogenic pathways mediated by vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and fibroblast growth factor receptors. Evidence about its efficacy in addition to second-line chemotherapy in non-small cell lung cancer (NSCLC) has been produced by two large randomized phase III clinical trials (LUME-Lung 1 and LUME-Lung 2), conducted in patients with pretreated NSCLC, without major risk factors for bleeding. In the LUME-Lung 1, the addition of nintedanib to docetaxel significantly improved progression-free survival, which was the primary end point of the trial (3.4 vs. 2.7 months, hazard ratio: 0.79;p= 0.0019). Furthermore, a significant improvement in median overall survival (from 10.3 to 12.6 months) was observed in patients with adenocarcinoma histology, with a greater advantage in patients who progressed within 9 months after start of first-line treatment (from 7.9 to 10.9 months) and in patients who were most refractory to first-line chemotherapy (from 6.3 to 9.8 months). Adverse events were more common in the docetaxel plus nintedanib group, and they included diarrhea and increased liver enzymes, while no statistically significant increase in the incidence of bleeding and hypertension events by the addition of nintedanib was observed. On these bases, the combination of docetaxel and nintedanib can be considered a new option for the second-line treatment for patients with advanced NSCLC with adenocarcinoma histology. Future challenges are the identification of predictive factors to help the decision of using nintedanib in eligible patients.
authors.affiliation: Thoracic Medical Oncology, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS , Napoli , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Manzo
authors.affiliation: Department of Oncology and Hematology, Azienda Ospedaliera Pugliese-Ciaccio , Catanzaro , Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Carillio
authors.affiliation: Thoracic Medical Oncology, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS , Napoli , Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Montanino
authors.affiliation: Thoracic Medical Oncology, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS , Napoli , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Costanzo
authors.affiliation: Thoracic Medical Oncology, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS , Napoli , Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sandomenico
authors.affiliation: Thoracic Surgery, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS , Napoli , Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Rocco
authors.affiliation: Thoracic Medical Oncology, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS , Napoli , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
keywords: NSCLC; VEGF; angiogenesis inhibitors; nintedanib; review