From the Journals

Mutations influence prognostic value of tumor location in stage III colon cancer



Among patients with resected stage III colon cancer, the prognostic value of primary tumor location varied according to patients’ BRAF or RAS mutational status, according to a post hoc analysis of patients in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 trial.

Specifically, in patients with BRAF or RAS mutations, disease-free survival (DFS) was better in right-sided vs. left-sided tumors, while in patients with RAS and BRAF double wild type, DFS was worse in right-sided vs. left-sided tumors, authors of the study reported in JAMA Oncology.

Right-sided tumor location has been associated with poor survival in previous studies of patients with metastatic colorectal cancer. However, for patients with stage III disease, such as those in this study, little is known about how tumor sidedness affects outcomes, the investigators wrote (JAMA Oncol. 2017 Nov 22. doi: 10.1001/jamaoncol.2017.3695).

“Although primary tumor location does not seem to be associated with DFS in the whole study population, opposite sidedness prognostic values are observed for RAS and BRAF wild-type and mutant tumors,” wrote Julien Taieb, MD, PhD, Department of Hepatogastroenterology and GI Oncology, Hôpital Européen Georges-Pompidou, Paris, and his coauthors.

The post hoc analysis included 1,869 resected stage III colon cancer patients with full information on primary tumor location in the PETACC-8 phase 3 randomized trial. The primary objective of the trial was to evaluate adjuvant treatment with the FOLFOX regimen with or without cetuximab.

Forty percent of the patients had a right-sided tumor, data show.

Right-sided tumor location was not prognostic for DFS for all patients, though it was associated with shorter survival after relapse (hazard ratio, 1.54; 95% confidence interval, 1.23-1.93; P = .001) and overall survival (HR, 1.25; 95%CI, 1.02-1.54; P = .03).

However, when looking at different molecular subgroups, Dr. Taieb and his colleagues found that DFS was better in right-sided vs. left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046), and similar findings were seen in BRAF-mutated tumors.

Conversely, DFS was worse in right-sided vs. left-sided tumors among those patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04), the investigators reported.

Investigators also sought to evaluate whether tumor location predicted the benefit of cetuximab.

However, “no benefit of adding cetuximab to FOLFOX was observed in our population of patients with stage III left-sided tumors, nor was any detrimental effect of adding cetuximab observed in right-sided tumors,” Dr. Taieb and his coauthors wrote.

PETACC-8 was sponsored by the Fédération Francophone de Cancérologie Digestive with some support from Merck KGaA and Sanofi-Aventis. Dr. Taieb reported participating in consulting or advisory boards for Merck KGaA, Sanofi, Roche/Genentech, Pfizer, and Amgen.

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