Published online Sep 15, 2016. doi: 10.4251/wjgo.v8.i9.642
Peer-review started: March 26, 2016
First decision: June 6, 2016
Revised: June 21, 2016
Accepted: July 20, 2016
Article in press: July 22, 2016
Published online: September 15, 2016
Colorectal cancer (CRC) is a significant cause of cancer-related morbidity and mortality all over the world. Improvements of cytotoxic and biologic agents have prolonged the survival in metastatic CRC (mCRC), with a median overall survival of approximately 2 years and more in the past two decades. The biologic agents that have proven clinical benefits in mCRC mainly target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). In particular, bevacizumab targeting VEGF and cetuximab and panitumumab targeting EGFR have demonstrated significant survival benefits in combination with cytotoxic chemotherapy in the first-line, second-line, or salvage setting. Aflibercept, ramucirumab, and regorafenib are also used in second-line or salvage therapy. Recent retrospective analyses have shown that KRAS or NRAS mutations were negative predictive markers for anti-EGFR therapy. Based on the evidence from large randomized clinical trials, personalized therapy is necessary for patients with mCRC according to their tumor biology and characteristics. The aim of this paper was to summarize the results of the major randomized clinical trials and highlight the benefits of the molecular targeted agents in patients with mCRC.
Core tip: The development of molecular targeted agents contributes to prolonging survival of patients with metastatic colorectal cancer (mCRC). One anti-vascular endothelial growth factor agent, bevacizumab, and two anti-epidermal growth factor receptor (EGFR) agents, cetuximab and panitumumab, have demonstrated clinical benefits in first-line, second-line, or salvage therapy in combination with cytotoxic chemotherapy. Moreover, RAS mutation has been proven to be a negative biomarker for anti-EGFR therapy in recent retrospective analyses. This article summarizes the evidence from large clinical trials and highlights the benefit of the molecular targeted agents in patients with mCRC.