A Phase III clinical trial has found that adding cetuximab (Erbitux) to standard adjuvant chemotherapy in patients with stage III colon cancer and normal KRAS gene activity does not help prolong their lives, and is associated with significantly more side effects. The study was terminated early due to these results. These findings are surprising because cetuximab was previously found to improve survival of patients with metastatic colon cancer whose tumors
expressed normal KRAS.

"This is a disappointing result. Given past success among patients with more advanced colon cancer, we had expected cetuximab to work in this setting. This study shows that this treatment should not be used in patients with resected stage III colon cancer," said lead researcher Steven Alberts, MD, professor of oncology at the Mayo Clinic College of Medicine in Rochester, Minn. Cetuximab is a monoclonal antibody that works by inhibiting the epidermal growth factor
receptor (EGFR). KRAS is a common signaling gene that transmits growth signals from EGFR.

In this randomized Phase III trial, researchers compared disease-free and overall survival between patients with stage III disease and normal KRAS activity who were randomly assigned to receive either FOLFOX alone (858 patients) or FOLFOX plus cetuximab (902 patients). After a median follow-up period of 15.9 months, researchers found that three-year, disease-free survival was similar in both groups (74.1 percent for FOLFOX alone versus 73.3 percent for
FOLFOX plus cetuximab). The FOLFOX-only group had slightly better overall survival (87.3 percent versus 82.1 percent). Patients 70 and older who received both FOLFOX plus cetuximab also fared worse than patients under 70 years old who received the same treatment. Moderate to severe side effects were significantly greater in the FOLXFOX plus cetuximab group, and fewer patients in this group were able to complete the full course of treatment due to these toxicities.


Source: ASCO