Risk of Recurrence in Stage III Colon Cancer According to RAS- and BRAF-Mutation Status

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In a study in the PETACC-8 trial population reported in JAMA Oncology, Julien Taieb, MD, PhD, of the Université Paris Descartes, and colleagues 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. 

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. 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.” ■

Taieb J, et al: JAMA Oncol. November 22, 2017 (early release online).




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