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KRAS BRAF V600E Mutations Impact Survival in Colon Cancer

Mutations linked to shorter survival in patients with microsatellite-stable tumors

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MONDAY, Jan. 18, 2016 (HealthDay News) -- For patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin (FOLFOX), KRAS and BRAF V600E mutations are associated with worse clinical outcome in patients with microsatellite-stable tumors, according to a study published online Jan. 14 in JAMA Oncology.

Julien Taieb, M.D., Ph.D., from the Paris Descartes University, and colleagues examined the prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer. They determined mismatch repair, BRAF V600E, and KRAS exon 2 mutational status in prospectively collected tumor blocks from 2,559 patients enrolled in the PETACC-8 phase III randomized trial, who were randomized to six months of FOLFOX4 or FOLFOX4 plus cetuximab.

The researchers found that 9.9 percent of participants had microsatellite instability (MSI) phenotype, 33.1 percent had KRAS mutation, and 9.0 percent had BRAF V600E mutation. In multivariate analysis, KRAS mutation correlated with shorter disease-free survival (DFS) and overall survival (OS) (hazard ratios, 1.55 and 1.56, respectively), while MSI and BRAF V600E were not prognostic. In subgroup analysis, independent associations for worse clinical outcomes were seen for patients with microsatellite-stable tumors with KRAS (hazard ratios for DFS and OS, 1.64 and 1.71, respectively) and BRAF V600E mutations (hazard ratios for DFS and OS, 1.74 and 1.84, respectively).

"BRAF V600E and KRAS mutations were significantly associated with shorter DFS and OS in patients with microsatellite-stable tumors but not in patients with MSI tumors," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including Merck and Sanofi, both of which supported the study and provided study medications.

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