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Aflibercept: A Review in Metastatic Colorectal Cancer

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Abstract

Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF), a key regulator of angiogenesis. It binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, and, thus, prevents them from binding to and activating their cognate receptors. In the USA and EU, intravenously administered aflibercept in combination with an infusion of leucovorin, fluorouracil and irinotecan (FOLFIRI) is approved for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after treatment with an oxaliplatin-containing regimen. The efficacy of aflibercept in this indication was assessed in a multinational, pivotal phase 3 trial (VELOUR), in which the approved regimen of aflibercept 4 mg/kg every 2 weeks plus FOLFIRI significantly prolonged median overall survival by 1.44 months compared with FOLFIRI alone (primary endpoint). The addition of aflibercept also significantly prolonged progression-free survival and significantly increased the objective response rate compared with FOLFIRI alone. Addition of aflibercept to FOLFIRI was associated with anti-VEGF-related adverse events and an increased incidence of FOLFIRI-related adverse events, but the tolerability of the combination was generally acceptable in this pre-treated population. The most common grade 3 or 4 adverse events with aflibercept plus FOLFIRI included neutropenia, diarrhoea and hypertension. In conclusion, aflibercept plus FOLFIRI is a useful treatment option for patients with metastatic colorectal cancer previously treated with an oxaliplatin-containing regimen, with or without bevacizumab.

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Acknowledgments

During the peer review process, the manufacturer of aflibercept was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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  1. Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand

    Yahiya Y. Syed & Kate McKeage

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  1. Yahiya Y. Syed
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Correspondence to Yahiya Y. Syed.

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The preparation of this review was not supported by any external funding.

Conflicts of interest

Yahiya Syed and Kate McKeage are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: A. Carrato, Medical Oncology Department, Alcala University, Madrid, Spain; V. V. Georgoulias, Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece; T. Yoshino, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa-shi, Japan.

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Syed, Y.Y., McKeage, K. Aflibercept: A Review in Metastatic Colorectal Cancer. Drugs 75, 1435–1445 (2015). https://doi.org/10.1007/s40265-015-0444-4

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