Colorectal Cancer Tumor Type Affects Cetuximab Response

Patients with KRAS codon 13-mutated tumors live longer than those with other KRAS mutations

TUESDAY, Oct. 26 (HealthDay News) -- Patients with colorectal cancer who have the KRAS codon 13-mutated tumor type respond better to treatment with cetuximab than patients with other KRAS-mutated tumor types, according to a study in the Oct. 27 issue of the Journal of the American Medical Association.

Wendy De Roock, M.D., of the University of Leuven in Belgium, and colleagues assembled data on 579 patients with chemotherapy-refractory colorectal cancer who received the anti-epidermal growth factor receptor monoclonal antibody cetuximab during 2001 to 2008 in one of seven clinical trials or in independent treatment. The researchers analyzed the pooled data to correlate KRAS codon 12- and codon 13-mutated tumor types with overall and progression-free survival. The researchers also studied the effects of the mutations in vitro in isogenic cell lines with wild-type KRAS, p.G12V, or p.G13D mutant alleles treated with cetuximab.

The investigators found that, compared to other KRAS tumor types, the patients with p.G13D-mutated tumors who were treated with cetuximab had longer overall survival (median, 7.6 versus 5.7 months), and longer progression-free survival (median, 4.0 versus 1.9 months). In vitro and mouse model analysis found that p.G13D-mutated cells and KRAS wild-type cells were sensitive to cetuximab, while p.G12V-mutated colorectal cells were insensitive.

"In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutated tumors. Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted," the authors write.

Several study authors disclosed financial ties to pharmaceutical companies.

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Jeff Muise

Jeff Muise

Updated on October 26, 2010

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