November 12, 2014
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KRAS status predicted time to recurrence in resected stage III colon cancer

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KRAS exon 2 mutations independently predicted shorter time to recurrence in patients with resected stage III distal colon cancer who received adjuvant therapy, according to results of a post-hoc analysis of data from a phase 3 trial.

The prognostic potential of KRAS mutations in patients with colon adenocarcinoma had not been established, so researchers strived to address that question as part of an ancillary study of the PETACC8 trial. The trial evaluated adjuvant FOLFOX chemotherapy with or without cetuximab (Erbitux; Bristol-Myers Squibb, Lilly) in patients with stage III colon cancer.

In the subanalysis, Helene Blons, PhD, of Georges Pompidou European Hospital in Paris, and colleagues assessed the prognostic value of KRAS exon 2 mutations on time to recurrence and DFS.

No differences in time to recurrence and DFS were observed between the two treatment arms in the PETACC8 trial, so both were pooled for analysis in the ancillary study. However, patients with BRAF-mutated cancers were excluded from the ancillary study.

Blons and colleagues identified KRAS mutations in 638 (38.5%) of the 1,657 eligible tumors. They determined KRAS mutations were associated with shorter time to recurrence (P<.001).

Compared with wild-type tumors, those with codon 12 mutations were significantly associated with shorter time to recurrence (HR=1.67; 95% CI, 1.35-2.04) independent of other covariates. However, codon 13 mutations were not significantly associated with shorter time to recurrence (HR=1.23; 95% CI, 0.85-1.79).

Researchers also determined KRAS genotype has different impact on recurrence (P=.02) and DFS (P=.042) based on tumor location.

A subgroup analysis showed KRAS only affected time to recurrence and DFS in distal tumors. Researchers observed a significantly increased risk for relapse among patients with KRAS codon 12 mutations (HR=1.96; 95% CI, 1.51-2.56) and a borderline significantly increased risk for relapse among patients with codon 13 mutations (HR=1.59; 95% CI, 1-2.56).

“Future clinical trials in the adjuvant setting should consider both the tumor location and KRAS mutations as important stratification factors,” Blons and colleagues wrote.

Disclosure: The researchers report research funding and honoraria from, advisory roles with or lecture roles with Amgen, Bayer, Bristol-Myers Squibb, Genomic Health, Lilly, Merck, Merck KGaA, Merck-Serono, Myriad Genetics, Pfizer, Roche and Sanofi.