Format

Send to

Choose Destination
Clin Cancer Res. 2014 Jun 1;20(11):3033-43. doi: 10.1158/1078-0432.CCR-13-3140. Epub 2014 Mar 31.

KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance).

Author information

1
Authors' Affiliations: Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota; Lehigh Valley Hospital, Allentown, Pennsylvania; and Ohio State University, Columbus, Ohio.
2
Authors' Affiliations: Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota; Lehigh Valley Hospital, Allentown, Pennsylvania; and Ohio State University, Columbus, Ohio sinicrope.frank@mayo.edu.

Abstract

PURPOSE:

We examined the prognostic impact of specific KRAS mutations in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF-wild-type tumors, because BRAF mutation was associated with poor prognosis, and BRAF and KRAS mutations are mutually exclusive.

EXPERIMENTAL DESIGN:

The seven most common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF-wild-type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were not predictive of adjuvant cetuximab benefit, study arms were pooled for analysis. Disease-free survival (DFS) was evaluated by HRs using Cox models.

RESULTS:

KRAS mutations in codon 12 (multivariate HR, 1.52; 95% confidence interval, CI, 1.28-1.80; P < 0.0001) or codon 13 (multivariate HR, 1.36; 95% CI, 1.04-1.77; P = 0.0248) were significantly associated with shorter DFS compared with patients with wild-type KRAS/BRAF tumors, independent of covariates. KRAS codon 12 mutations were independently associated with proficient mismatch repair (P < 0.0001), proximal tumor site (P < 0.0001), low grade, age, and sex, whereas codon 13 mutations were associated with proximal site (P < 0.0001).

CONCLUSION:

KRAS mutations in either codon 12 or 13 are associated with inferior survival in patients with resected stage III colon cancer. These data highlight the importance of accurate molecular characterization and the significant role of KRAS mutations in both codons in the progression of this malignancy in the adjuvant setting. Clin Cancer Res; 20(11); 3033-43. ©2014 AACR.

PMID:
24687927
PMCID:
PMC4040326
DOI:
10.1158/1078-0432.CCR-13-3140
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Supplementary concept, Grant support

Publication types

MeSH terms

Substances

Supplementary concept

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center