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Int. J. Mol. Sci. 2017, 18(10), 2021;

Angiogenesis Inhibitors in NSCLC

Thoracic Medical Oncology, Istituto Nazionale Tumori, “Fondazione G.Pascale”—IRCCS, 80131 Napoli, Italy
Department of Oncology and Hematology, Azienda Ospedaliera Pugliese-Ciaccio, 88100 Catanzaro, Italy
Cellular Biology and Biotherapy, Research Department, Istituto Nazionale Tumori “Fondazione G.Pascale”—IRCCS, Napoli 80131, Italy
Clinical Trials Unit, Istituto Nazionale Tumori, “Fondazione G.Pascale”—IRCCS, 80131 Napoli, Italy
Thoracic Surgery, Istituto Nazionale Tumori, “Fondazione G.Pascale”—IRCCS, 80131 Napoli, Italy
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 26 July 2017 / Revised: 13 September 2017 / Accepted: 15 September 2017 / Published: 21 September 2017
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Angiogenesis is a complex biological process that plays a relevant role in sustaining the microenvironment, growth, and metastatic potential of several tumors, including non-small cell lung cancer (NSCLC). Bevacizumab was the first angiogenesis inhibitor approved for the treatment of patients with advanced NSCLC in combination with chemotherapy; however, it was limited to patients with non-squamous histology and first-line setting. Approval was based on the results of two phase III trials (ECOG4599 and AVAIL) that demonstrated an improvement of about two months in progression-free survival (PFS) in both trials, and in the ECOG4599 trial, an improvement in overall survival (OS) also. Afterwards, other antiangiogenic agents, including sunitinib, sorafenib, and vandetanib have been unsuccessfully tested in first and successive lines. Recently, two new antiangiogenic agents (ramucirumab and nintedanib) produced a significant survival benefit in second-line setting. In the REVEL study, ramucirumab plus docetaxel prolonged the median OS of patients with any histology NSCLC when compared with docetaxel alone (10.4 versus 9.1 months, hazard ratio (HR) 0.857, p = 0.0235). In the LUME-Lung 1 study, nintedanib plus docetaxel prolonged the median PFS of patients with any tumor histology (p = 0.0019), and improved OS (12.6 versus 10.3 months) in patients with adenocarcinoma. As a result, it became a new option for the second-line treatment of patients with advanced NSCLC and adenocarcinoma histology. Identifying predictive biomarkers to optimize the benefit of antiangiogenic drugs remains an ongoing challenge. View Full-Text
Keywords: angiogenesis; vascular endothelial growth factor (VEGF); bevacizumab; nintedanib; ramucirumab; VEGF trap angiogenesis; vascular endothelial growth factor (VEGF); bevacizumab; nintedanib; ramucirumab; VEGF trap

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Manzo, A.; Montanino, A.; Carillio, G.; Costanzo, R.; Sandomenico, C.; Normanno, N.; Piccirillo, M.C.; Daniele, G.; Perrone, F.; Rocco, G.; Morabito, A. Angiogenesis Inhibitors in NSCLC. Int. J. Mol. Sci. 2017, 18, 2021.

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