The addition of Erbitux® (cetuximab) to standard adjuvant chemotherapy in patients with stage III colon cancer who have normal KRAS gene activity does not improve survival, according to the results of a Phase III study presented at the 2010 annual meeting of the American Society of Clinical Oncology.
Stage III colon cancer refers to cancer that has spread to lymph nodes surrounding the colon but not to other parts of the body.
Erbitux is a targeted therapy that inhibits growth of the cancer by binding to a portion of the epidermal growth factor receptor (EGFR), a protein located on the surface of many cancer cells. Erbitux is currently approved for the treatment of selected patients with advanced head and neck cancer or advanced colorectal cancer.
Among patients with metastatic colorectal cancer, response to Erbitux appears to vary by whether or not the tumor contains a mutation in a gene known as KRAS. Erbitux does not appear to benefit patients with KRAS gene mutations, but has been found to benefit patients with normal KRAS. This benefit among patients with metastatic colorectal cancer and normal KRAS prompted interest in the role of Erbitux among patients with earlier-stage colorectal cancer and normal KRAS.
The Phase III study involved 1,760 patients with stage III colon cancer and normal KRAS who were randomized to receive either the chemotherapy regimen FOLFOX alone or FOLFOX plus Erbitux. After a median follow-up of 15.9 months, the results indicated that the three-year disease-free survival was similar between the two groups. The FOLFOX group had slightly better overall survival (87.3%) compared with the FOLFOX plus Erbitux group (82.1%).
Patients who received the combination of Erbitux and FOLFOX experienced a significantly higher rate of moderate to severe side effects and as a result, fewer patients in this group were able to complete the full course of treatment.
The researchers concluded that although Erbitux has previously been shown to improve survival in patients with metastatic colon cancer with normal KRAS gene activity, the same does not appear to be true in stage III colon cancer. Furthermore, the treatment was associated with significantly more side effects.
Reference: Alberts SR, Sargent DJ, Smyrk TC, et al. Adjuvant mFOLFOX6 with or without cetuximab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): Results from NCCTG Intergroup phase III trial N0147. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract CRA 3507