KRAS mutation status identifies likely cetuximab benefit in colorectal cancer

STOCKHOLM (Reuters Health) - KRAS mutation status is an excellent predictor of clinical outcome in patients with metastatic colorectal cancer undergoing first-line treatment with cetuximab plus the irinotecan-based regimen FOLFIRI, researchers reported at the 33rd Congress of the European Society for Medical Oncology (ESMO).

Dr. Eric Van Cutsem, with University Hospital Gasthuisberg in Leuven, Belgium, and associates reviewed the impact of KRAS mutation status on multiple outcome measures in 540 patients assigned to first-line cetuximab combined with FOLFIRI or FOLFIRI alone in the phase III CRYSTAL trial.

An earlier analysis of the data showed that the combination of cetuximab and FOLFIRI significantly improved overall progression-free survival and the response rate.

For the current study, the research team isolated genomic DNA from archived tumor material and determined KRAS mutation status on codons 12/13 using a quantitative PCR-based assay.

Wild-type KRAS was identified in 65% of tumors and mutant KRAS in 35%.

An assessment of outcome by KRAS mutation status showed that the addition of cetuximab to FOLFIRI produced large benefits in patients with KRAS wild-type tumors. There was a decreased risk of disease progression (HR=0.68), an increase in response rates from 43% to 59%, and an increase of 4 months in overall survival (21.0 months for KRAS mutant tumors and 24.9 months for KRAS wild-type tumors, HR=0.84).

Patients with KRAS mutant tumors did not benefit from the combination of cetuximab and FOLFIRI.

"Analyzing KRAS mutation status is the first example of molecular driven selection in colorectal cancer and opens a new era of tailored treatment strategies," Dr. Van Cutsem said at a news conference. Accordingly, he called for KRAS testing in newly diagnosed patients with metastatic colorectal cancer and added that results of the assay are usually available within a week, thereby allowing prompt initiation of treatment.

He told Reuters Health that research is presently underway to identify additional predictors of treatment outcomes besides KRAS status in patients with metastatic colorectal cancer.

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