In a recent study titled “Prognostic value of KRAS mutations in stage III colon cancer: post-hoc analysis of the PETACC8 phase III trial dataset”, published in the journal Annals of Oncology, a team of researchers led by Helene Blons, PhD, Georges Pompidou European Hospital, Paris, France, analyzed data from a Phase 3 clinical trial (PETACC8) and demonstrated that KRAS exon 2 mutations can independently predict shorter time to recurrence in patients with resected stage III distal colon cancer who received adjuvant therapy.
The research team wanted to understand what was the prognostic potential of KRAS mutations in patients with colon adenocarcinoma, so they looked at data from the PETACC8 trial, which assessed adjuvant FOLFOX chemotherapy with or without cetuximab in patients with stage III colon cancer.
The results of the trial showed no differences in time to recurrence and disease free survival between the two groups, as such, all subjects (apart from those with BRAF-mutated cancers) were included in Dr. Blons’s study.
This ancillary analysis demonstrated a KRAS mutation rate of 38.5% among the total 1,657 tumors analyzed, which was directly associated with shorter time to recurrence.
When the team compared wild-type tumors to KRAS-positive tumors, they saw that those with codon 12 mutations were significantly associated with shorter time to recurrence.
Furthermore, depending on tumor location, a KRAS genotype could have different recurrence and disease free survival outcomes.
After preforming a subgroup analysis in a total of 1043 tumors (692 wild type; 351 mutated), the team showed that KRAS only impacted time to recurrence and disease free survival in distal tumors, with an increased risk of relapse for codon 12 mutations and a borderline significance for codon 13 mutations.
The authors conclude in their study that KRAS exon 2 mutations are independent predictors of shorter time to recurrence in patients diagnosed with resected stage III distal colon cancers who receive adjuvant therapy. “Future clinical trials in the adjuvant setting should consider both the tumor location and KRAS mutations as important stratification factors”, they conclude.
