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KRAS status predicts response to Cetuximab for Metastatic Colorectal Cancer.


Patients with advanced colorectal cancer who do not have mutant forms of the gene KRAS in their tumors are most likely to benefit from the monoclonal antibody cetuximab (Erbitux[R], ImClone Systems Inc.) and chemotherapy, compared to patients who have tumors that contain a mutated form of the gene, according to a new study presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL (Van Cutsem et al., 2008). This means that patients whose tumors have the mutant form of the gene should not receive the treatment because they are unlikely to benefit from it and should be spared the side effects and the cost.

This research and other findings presented at ASCO meeting has led experts to predict that it will become standard practice to test all colorectal tumors for KRAS mutation before starting patients on therapies involving cetuximab and a similar drug, panitumumab (Vectibix[R], Amgen Inc.). These drugs are designed to block the activity of the epidermal growth factor receptor protein, which is often overactive in colorectal cancer. An estimated 30%-40% of colorectal tumors carry KRAS mutations.

The new results were based on an analysis of archived tumor samples from 587 of the 1,198 patients in the CRYSTAL study, which had previously shown that some patients with metastatic disease benefited from cetuximab plus chemotherapy with respect to progression-free survival. Growing interest in the KRAS gene led researchers to reevaluate the tumor tissue samples based on whether tumors showed normal or mutant KRAS expression. The KRAS mutation was detected in 192 samples. The 36% frequency was similar to the KRAS mutational frequency observed in other studies.

Of the 348 tumor samples that expressed normal KRAS, one-year progression-free survival rates were 25% and 43% for patients with normal KRAS tumors receiving FOLFIRI (fluorouracil, leucovorin, and irinotecan) and the combination of cetuximab plus FOLFIRI, respectively. Median progression-free survival also improved for patients receiving cetuximab and FOLFIRI in the presence of normal KRAS tumors (9.9 months versus 8.7 for FOLFIRI alone). Overall, the increase in the objective response rate was highly significant for patients who received cetuximab in combination with FOLFIRI (59.3% versus 43.2% for patients receiving FOLFIRI alone).

When clinical response was reevaluated for the 192 patients whose tumors had the KRAS mutation, overall responses and progression-free survival were similar whether patients received FOLFIRI or FOLFIRI plus cetuximab. Adding cetuximab to FOLFIRI did not improve clinical responses.

The findings supported results from other studies. Retrospective analysis of KRAS gene status and treatment outcomes have been preformed on 1,200 patients with advanced colorectal cancer in separate randomized trials. Prospective studies are now needed to validate the marker.

Van Custem, E., Lang, I., D'haens, G., Moiseyenko, V., Zaluski, J., Folprecht, G., et al. (2008, May). Rougier KRAS status and efficacy in the first line treatment of patients with metastatic colorectal cancer (MCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience [Abstract 2]. Presented at the annual meeting of the American Society of Clinical Oncology, Chicago, IL.

Deborah McBride, RN, MSN, CPON[R], Contributing Editor

Contributing Editor Deborah McBride, RN, MSN, CPON[R], is a nurse at the Kaiser Permanente Oakland Medical Center and a faculty member at Samuel Merritt College in Oakland, CA.
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Author:McBride, Deborah
Publication:ONS Connect
Geographic Code:1U9CA
Date:Aug 1, 2008
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