ASCO 2014 Report – KRAS exon 2 gene mutations appear to predict time to recurrence or disease-free survival in stage III colon cancer

by Bruce Sylvester – KRAS exon 2 mutations are independent predictors of time to recurrence or disease-free survival among patients with stage III distal colon cancer who are receiving adjuvant therapy.

Researchers reported these findings in a poster presentation at ASCO 2014

As background, the authors noted that, “Prognostic value of KRAS mutations in resected colon adenocarcinoma remains debated. We examined the prognostic impact of KRAS exon 2 mutations in stage III patients receiving adjuvant FOLFOX + /- cetuximab patients from the PETACC8 Phase III trial.”

The investigators studied KRAS exon 2 mutations in codon 12 (p.G12V, p.G12R, p.G12S, p.G12A, p.G12C, p.G12D) and codon 13 (p.G13D) in all subjects with available material who had signed translational research informed consent for the trial.

They restricted the analyses to BRAF wild type tumors, “since the prognostic impact of BRAFV600E in this population has already been described,” they said.

No benefit or deleterious effect from adjuvant cetuximab had been previously reported in this trial, so tumors from both study arms were pooled for the analysis.

They evaluated for association between time to recurrence (TTR) and disease-free survival (DFS) and type of KRAS mutation.

They found KRAS mutations in 638/1657 tumors, including 502 codon 12 and 136 codon 13 alterations.

When compared to patients with KRAS/BRAF wild-type tumors, and independent of other covariates, patients with KRAS mutations in codon 12 (HR: 1.67; 95% confidence interval [CI] [1.35-2.04]; P<0.001) but not in codon 13 (HR: 1.23; 95% confidence interval [CI] [0.85-1.79]; P=0.26) were significantly more likely to have shorter time to recurrence.

The findings were similar for disease-free survival.

Taking anatomic sites into account, the impact of KRAS mutations on time to recurrence was found only for distal tumors (n=1043). Compared to KRAS/BRAF wild type patients, there was a significantly increased risk of relapse (HR: 1.96; 95% confidence interval [CI] [1.51-2.56]; P<0.0001) for KRAS codon 12 mutated tumors and a trend for codon 13 (HR: 1.59; 95% confidence interval [CI] [1.00-2.56]; P=0.051).

They found similar results for disease-free survival.

“Future clinical trials in the adjuvant setting should consider tumor location and type of KRAS mutation as important stratification factors,” the authors concluded.

Citation: 2014 ASCO Annual Meeting: General Poster Session, Gastrointestinal (Colorectal) Cancer; Abstract Number 3549