Incidence of KRAS status in ongoing adjuvant trials in colon cancer

The current standard for adjuvant treatment of stage III colon cancer is chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin for 6 months. Cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is effective and safe in combination with an oxaliplatin-based regimen in patients with metastatic colorectal cancer. Based on these data, two large randomized, multicenter, phase 3 trials opened in 2005 to compare the efficacy of cetuximab combined with chemotherapy with that of chemotherapy alone in curatively R0 resected stage III colon cancer. The primary end point of these two trials is disease-free survival. The recent findings on tumor KRAS mutational status and efficacy of cetuximab in the metastatic setting have led to amendments to the protocols of both trials to enroll only patients with wild-type KRAS tumors. As a consequence, the sample sizes have increased and both trials will enroll more than 6000 patients in nine European countries and the United States. The first interim analyses are planned for 2011. This review summarizes current knowledge regarding stage III colon cancer adjuvant therapy, anti-EGFR therapy, KRAS status and its prognostic and predictive value in advanced colorectal cancer, and how to deal with these new scientific paradigms in the adjuvant setting.