New drug: Zaltrap – pro

Zaltrap was approved by the FDA in the beginning of August 2012 for patients who fail oxaliplatin. It is also known as aflibercept, VEGF trap or, when used for macular degeneration, Eylea. It is a recombinant fusion protein between the Fc portion of human IgG1 and the extracellular domains of VEGF receptor 1 & 2 (VEGFR 1 & VEGFR 2), which binds VEGF-A and VEGF-B (vascular endothelial growth factor), as well as PLGF (placental growth factor). By binding to and inhibiting these angiogenic growth factors, their neovascular activity, and vascular permeability, ziv-aflibercept inhibits tumor angiogenesis.

Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. The approval for colon cancer was based on a phase III trial. ZALTRAP, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is indicated for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen.

Aflibercept failed its primary endpoint of overall survival in the Vital phase III trial for second-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), although it improved the secondary endpoint of progression-free survival. It is also in trials for prostate cancer.

J. Tabernero, E. Van Cutsem, R. Lakomy, J. Prausova, P. Ruff, G. Van Hazel, V. Moiseyenko, D. Ferry, J. McKendrick, K. Soussan-Lazard, E. Boelle, C. Allegra. VELOUR, a Phase 3 Study of Aflibercept (A) Versus Placebo (pbo) in Combination with FOLFIRI for the Treatment of Patients (pt) with Previously Treated Metastatic Colorectal Cancer (MCRC). 2011 European Multidisciplinary Congress. Abstract 6LBA. Presented September 25, 2011.

Tzu-Fei Wang and Albert Craig Lockhart Aflibercept in the Treatment of Metastatic Colorectal Cancer Clin Med Insights Oncol. 2012; 6: 19–30.

Tang P, Cohen SJ, Bjarnason GA. Phase II trial of aflibercept (VEGF Trap) in previously treated patients with metastatic colorectal cancer (MCRC): a PMH phase II consortium trial. J Clin Oncol. 2008;(Suppl 26):Abstr 4027.

Teng LS, Jin KT, He KF, Zhang J, Wang HH, Cao J. Clinical applications of VEGF-trap (aflibercept) in cancer treatment. J Chin Med Assoc. 2010;73:449–56.

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