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Antiangiogenic therapy—evolving view based on clinical trial results

Abstract

Antiangiogenic therapies that target VEGF or its receptors have become a mainstay of cancer therapy in multiple malignancies. However, the clinical efficacy of these agents is less than originally anticipated and, in most settings, requires the addition of cytotoxic chemotherapy suggesting that, as for other targeted therapies, VEGF inhibitors will require selection of patient subpopulations to achieve maximal clinical benefit. Without the identification and use of predictive biomarkers for VEGF-targeted agents, and other agents that target the vasculature, further improvements in current clinical outcomes are unlikely. Exciting new data presented in 2011 at the ESMO conference showed that retrospective evaluation of plasma concentrations of VEGF-A predicted progression-free survival and/or overall survival benefit from bevacizumab in phase III trials in certain tumour types; prospective evaluation of the assay is required. This endeavour should be followed by further biomarker research, requiring inter-laboratory collaboration and high-quality, adequately powered clinical trials.

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Figure 1: Success rate for randomised, phase II or phase III clinical trials of the anti-VEGF monoclonal antibody bevacizumab or the VEGFR TKIs sunitinib, sorafenib and pazopanib.

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All the authors contributed to researching data for the article, discussion of content, and to writing and editing the article prior to submission.

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Correspondence to Gordon C. Jayson.

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G. C. Jayson receives grant/research support from AstraZeneca, Genentech and Roche. He has sat on advisory boards for AstraZeneca, Aveo, Genentech, Merck and Roche. D. J. Hicklin is a stock holder at Merck. L. M. Ellis declares that he serves as an ad hoc consultant for Genentech/Roche and Sanofi-Aventis.

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Jayson, G., Hicklin, D. & Ellis, L. Antiangiogenic therapy—evolving view based on clinical trial results. Nat Rev Clin Oncol 9, 297–303 (2012). https://doi.org/10.1038/nrclinonc.2012.8

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