A retrospective on the inhibition of epidermal growth factor receptor as a therapeutic strategy for patients with relapsed metastatic colorectal cancer: impact on treatment of today's patients.
The epidermal growth factor receptor (EGFR) pathway is overexpressed in many colorectal cancers (CRCs) and is associated with a worse prognosis compared with tumors that do not express EGFR. The development of monoclonal antibodies against this receptor, including cetuximab and panitumumab, and small-molecule inhibitors against the tyrosine kinase protein has led to new therapeutic paradigms in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibody cetuximab has been shown to reverse chemotherapy resistance in patients with irinotecan-refractory mCRC, to improve survival compared with best supportive care (BSC) alone, and to prolong progression free-survival (PFS) in the first- and second-line settings. Panitumumab prolongs PFS compared with BSC, and trials in the first- and second-line settings are ongoing. Clinical trials with tyrosine kinase inhibitors have yielded disappointing results. This article reviews the clinical trial evidence for treatment strategies based on EGFR inhibition in relapsed/refractory mCRC, mechanisms of resistance to EGFR agents, clinical uncertainties, and future directions.
Jackson
Christopher
C
Gastrointestinal and Lymphoma Units, Royal Marsden Hospital London and Surrey, United Kingdom.
Cunningham
David
D
D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D000077146:Irinotecan; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D000077544:Panitumumab; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000077544:Panitumumab; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin