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Review
. 2017 Sep 21;18(10):2021.
doi: 10.3390/ijms18102021.

Angiogenesis Inhibitors in NSCLC

Anna Manzo  1 , Agnese Montanino  2 , Guido Carillio  3 , Raffaele Costanzo  4 , Claudia Sandomenico  5 , Nicola Normanno  6 , Maria Carmela Piccirillo  7 , Gennaro Daniele  8 , Francesco Perrone  9 , Gaetano Rocco  10 , Alessandro Morabito  11
Affiliations
Review

Angiogenesis Inhibitors in NSCLC

Anna Manzo et al. Int J Mol Sci. .

Abstract

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.

Keywords: VEGF trap; angiogenesis; bevacizumab; nintedanib; ramucirumab; vascular endothelial growth factor (VEGF).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of action of angiogenesis inhibitors targeting VEGF, EGF, PDGF, FGF, RET and their receptors for suppressing angiogenesis. VEGF: vascular endothelial growth factor; EGF: epidermal growth factor; PDGF: placenta-derived growth factor; FGF: fibroblast growth factor; RET: REarranged during Transfection (gene).
See this image and copyright information in PMC

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