K-Ras Plus Disease Location Affect Colon Cancer Recurrence Time

K-Ras mutations may influence time to recurrence only in colon cancer patients with distal disease

medwireNews: Post-hoc trial analysis suggests a complex relationship between K-Ras Mutations and tumour location and their impact on the outcome of patients with stage III colon cancer.

Data from PETACC8, a phase III trial comparing FOLFOX 4 chemotherapy alone or alongside cetuximab, showed that, among the 1657 patients without a BRAF mutation, 38.5% carried a K-Ras mutation. The majority (79%) of K-Ras mutations were located on Codon 12.

Interaction analysis showed that patients with a K-Ras mutation had a significantly shorter time to recurrence (TTR) than those without (hazard ratio [HR]=1.56) and a higher rate of relapse (30 vs 19%).

Further investigation indicated that several K-Ras mutations in codon 12 were associated with shorter TTR (HR=1.67), whereas this was not the case for K-Ras mutations in codon 13 (p.G13D, HR=1.23), report Julien Taieb, from Georges Pompidou Hospital in Paris, France, and co-authors in the Annals of Oncology.

Both the codon 12 K-Ras mutations and the codon 13 variant were more common in patients with proximal than distal colon tumours. However, subgroup analysis showed that codon 12 mutations only significantly influenced TTR and disease-free survival in distal colon tumour patients, with a 1.96-fold increased risk of relapse. The codon 13 mutation had a borderline significance on the risk of relapse in patients with distal disease.

“The impact of the p.G13D mutation needs to be refined in a larger series according to tumor location and tumor phenotype ([microsatellite stable/Microsatellite instability]) although this study suggests that p.G13D distal [colorectal cancer] might behave as p.G12X tumors”, the team comments.

The authors conclude: “Future clinical trials in stage III colon cancer should consider both the tumor location and K-Ras mutational status as important stratification factors.”


Blons H, Emile J, Le Malicot K, et al. Prognostic value of KRAS mutations in stage III colon cancer: post-hoc analysis of the PETACC8 phase III trial dataset. Ann Oncol 2014; First published online 6 October. doi: 10.1093/annonc/mdu464

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