Abstract
There is a major unmet medical need for effective and well-tolerated treatment options for patients with advanced nonsmall cell lung cancer (NSCLC), in both first-line and relapsed/refractory settings. Experimental evidence has validated signalling pathways that regulate tumour angiogenesis, including the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways, as valid anti-cancer drug targets. However, to date, bevacizumab (an anti-VEGF monoclonal antibody) is the only antiangiogenic agent to be approved for the treatment of NSCLC. Many other agents, including antibodies, small-molecule tyrosine kinase inhibitors and vascular disrupting agents, have been assessed in phase III trials but have generally failed to demonstrate clinically meaningful benefits. This lack of success probably reflects the redundancy of proangiogenic pathways and the molecular and clinical heterogeneity of NSCLC.
In this review we summarise recently completed and ongoing randomised clinical trials of emerging antiangiogenic agents in patients with NSCLC. We highlight recent promising data with agents that simultaneously inhibit multiple proangiogenic pathways, including the PDGF and FGF pathways, as well as the VEGF pathway. Finally, we discuss the outlook for antiangiogenic agents in NSCLC, emphasising the need for clinically validated prognostic and predictive biomarkers to identify patients most likely to respond to therapy.
Footnotes
Provenance: Publication of this peer-reviewed article was supported by Boehringer Ingelheim, Germany (article sponsor, European Respiratory Review issue 131).
Conflict of interest: None declared.
- Received December 10, 2013.
- Accepted December 19, 2013.
- ©ERS 2014
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