Primary Tumor Location and Outcomes in Stage III Colon Cancer According to RAS- and BRAF-Mutation Status


Key Points

  • Disease-free survival was better in patients with right-sided vs left-sided colorectal tumors who had RAS mutations.
  • Disease-free survival was poorer in patients with right-sided vs left-sided colorectal tumors who had both RAS and BRAF wild-type tumors.


In a study in the PETACC-8 trial population reported in JAMA Oncology, Taieb et al found that the risk of recurrence in patients with stage III colon cancer differed for the primary tumor location according to RAS- and BRAF-mutation status.

Study Details

A total of 2,559 patients were randomized to receive adjuvant FOLFOX (leucovorin, fluorouracil, and oxaliplatin) with or without cetuximab (Erbitux). Of them, 1,900 were screened by next-generation sequencing, with the primary tumor location identified in 1,869. Among them (57% male), 755 (40%) had a right-sided tumor, 164 (10%) had microsatellite instability (MSI), 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations.


Among all patients, there was no significant difference in disease-free survival for right-sided vs left-sided tumors. However, survival after relapse (hazard ratio [HR] = 1.54, P = .001) and overall survival (HR = 1.25, P = .03) were better for left-sided tumors, with 5-year rates of 31.1% vs 18.5% and 84.2% vs 78.6%, respectively.

No significant difference in disease-free survival was observed between patients with microsatellite-stable vs MSI tumors. For right-sided vs left-sided tumors, disease-free survival was better among those with RAS mutations (HR = 0.80, P = .046) and worse for those with RAS and BRAF double wild-type tumors (HR = 1.39, P = .04). A trend toward improved disease-free survival for right-sided tumors was also observed in patients with BRAF mutations. These outcomes were independent of the treatment received. No benefit of cetuximab on disease-free or overall survival was observed among patients with left-sided tumors.

The investigators concluded: “Although right-sided tumor location is associated with poor survival in patients with metastatic [colon cancer] as previously reported, the association with disease recurrence appears to vary for patients with stage III [colon cancer] and RAS or BRAF mutations vs those with double wild type.”

Financial support for study management was provided by Merck KGaA.

Julien Taieb, MD, PhD, of the Université Paris Descartes, is the corresponding author of the JAMA Oncology article.

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