Why do targeted agents not work in the adjuvant setting in colon cancer?

The standard adjuvant treatment of stage III and high-risk stage II colon cancer is to administer 6 months of oxaliplatin- and fluorouracil-containing chemotherapy. However, nearly a third of stage III patients still recur. The positive results of cetuximab and bevacizumab added to chemotherapy in patients with metastatic colorectal cancer formed the basis to explore the role of these agents in the adjuvant setting. However, two adjuvant trials with bevacizumab and one adjuvant trial with cetuximab have failed to show any benefit of adding these agents to standard chemotherapy. Although reasons for the negative results remain unknown, the divergent effects of bevacizumab and cetuximab in early- versus advanced stage colon-cancer reinforce the notion that adjuvant and metastatic settings represent distinct diseases that require different treatments. This article summarizes the results of the adjuvant bevacizumab and cetuximab trials and discusses the possible explanations why molecularly targeted agents had no impact on improving the outcomes of adjuvant treatment of colon cancer.