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Gastrointestinal Cancer

The Evolving Role of Monoclonal Antibodies in Colorectal Cancer: Early Presumptions and Impact on Clinical Trial Development

The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Key Words. Cetuximab • Bevacizumab • Panitumumab • EGFR • VEGF • Colorectal

Correspondence: Cathy Eng, M.D., F.A.C.P., The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, 1515 Holcombe Blvd, Box 0426, Houston, Texas 77030, USA. Telephone: 713-792-8146; Fax: 713-794-1873; e-mail: ceng{at}mdanderson.org

Received July 27, 2009; accepted for publication December 8, 2009; first published online in THE ONCOLOGIST Express on January 12, 2010.

Disclosures: Cathy Eng: Honoraria: Pfizer, Roche; Research funding/contracted research: Genentech, BMS, Amgen, Sanofi-Aventis.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plateau of FDA-approved agents for the treatment of mCRC, pivotal results have developed that critically affect the care for these patients. Correlative data from randomized trials of EGFR inhibitors across disease settings have demonstrated higher response rates, specifically for patients with wild-type K-RAS tumors. The interpretation of the B-RAF mutation and other molecular markers may further define the appropriateness of anti-EGFR therapy. Recent literature revealed that the first-line use of combined anti-EGFR therapy plus bevacizumab resulted in inferior outcomes and additional toxicities. Furthermore, the role of biologic agents for locally advanced colon cancer cannot be advocated at this time. With impending changes in the health care system, the economic impact of mAbs will continue to be scrutinized. Hence, as the significance of molecular markers continues to develop, their role as it pertains to the appropriate use of biologic agents in the treatment of mCRC will continue to evolve.