KRAS status predicted cetuximab benefit

Cetuximab monotherapy was not an effective treatment for patients with advanced colorectal cancer bearing mutated KRAS tumors, but was effective for those with wild-type KRAS tumors in a study recently published in The New England Journal of Medicine.

Christos Karapetis, MD, from Flinders University in Australia, and his colleagues from the National Cancer Institute of Canada and the Australasian Gastro-Intestinal Trials Group assessed KRAS mutation status in 394 patients. Patients were randomly assigned to receive intravenous cetuximab (Erbitux, ImClone) once a week plus best supportive care or best supportive care alone. Forty percent of patients had cancers with mutations in KRAS; 60% had wild-type KRAS.

Patients with mutated KRAS had a median OS of 4.6 months on cetuximab vs. 4.5 months with best supportive care. “When we looked at patients with cancers with mutations in KRAS and compared the group that received cetuximab and the group with best supportive care we could see no difference,” Karapetis said when he presented the study findings in September at the 33rd Congress of the European Society for Medical Oncology. “Cetuximab did not provide any advantage.”

However, those patients with wild-type KRAS had a median OS of 9.5 months on cetuximab vs. 4.8 months with best supportive care (P<.0001).

Patients with mutated KRAS had a median PFS of 1.8 months in both arms of the trial. Those patients with wild-type KRAS who were treated with cetuximab had a median PFS of 3.7 months vs. 1.9 months with best supportive care.

The researchers also examined whether KRAS status had a prognostic effect and found that “in this particular setting there was no prognostic impact of the KRAS status.”

For more information:

N Engl J Med. 2008;359:1757-1765.

Karapetis C. #LBA6. Presented at: the 33rd Congress of the European Society for Medical Oncology; Sept. 12-16, 2008; Stockholm.