Ziv-aflibercept: A novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer
- 1 November 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in American Journal of Health-System Pharmacy
- Vol. 70 (21), 1887-1896
- https://doi.org/10.2146/ajhp130143
Abstract
Purpose The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of ziv-aflibercept in combination therapy for metastatic colorectal cancer (mCRC) are reviewed. Summary Ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion protein that targets the angiogenesis signaling pathway of tumor cells by blocking vascular endothelial growth factor (VEGF) receptors that play a key role in tumor growth and metastasis; it is a more potent VEGF blocker than bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI regimen) for second-line treatment of patients with mCRC who have disease progression during first-line oxaliplatin-based chemotherapy. A Phase III trial demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept was associated with significantly improved patient response, overall survival, and progression-free survival in patients with good performance status at baseline, including some who had received prior bevacizumab therapy. The most common grade 3 or 4 adverse effects associated with ziv-aflibercept use in clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product labeling warns of potential hemorrhage and other treatment-related risks. Conclusion Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.Keywords
This publication has 46 references indexed in Scilit:
- A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancerInvestigational New Drugs, 2012
- Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based RegimenJournal of Clinical Oncology, 2012
- Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid TumorsClinical Cancer Research, 2012
- Tyrosine Kinase Receptor Flt/VEGFR Family: Its Characterization Related to Angiogenesis and CancerGenes & Cancer, 2010
- Initial Assessment, Surveillance, and Management of Blood Pressure in Patients Receiving Vascular Endothelial Growth Factor Signaling Pathway InhibitorsJNCI Journal of the National Cancer Institute, 2010
- Phase I Study of Intravenous Vascular Endothelial Growth Factor Trap, Aflibercept, in Patients With Advanced Solid TumorsJournal of Clinical Oncology, 2010
- Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal CancerThe New England Journal of Medicine, 2009
- Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III StudyJournal of Clinical Oncology, 2008
- VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockadeProceedings of the National Academy of Sciences of the United States of America, 2007
- A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal CancerJournal of Clinical Oncology, 2004