Taieb J, et al. - This post hoc analysis was performed to ascertain the prognostic and predictive value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients with stage III colon cancer (CC) receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab. As previously reported, right-sided tumor location was correlated with poor survival in patients with metastatic CC. However, the association with disease recurrence appeared to vary for patients with stage III CC and RAS or BRAF mutations vs those with double wild type.

Methods

• The researchers included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial.
• During this study, 2,559 patients underwent randomization.
• Out of these patients, 1,900 were screened by next-generation sequencing, which demonstrated that 1,869 had full information concerning PTL.
• Primary tumor site was categorized as located proximal (right) or distal (left) to the splenic flexure.
• They evaluated the associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status.

Results

• In this study, 755 patients (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations, among the 1,869 subjects (1,056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed.
• In the whole population, right-sided tumor location was not prognostic for DFS but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P=.001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P=.03).
• The researchers found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P=.046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P=.04), when looking at DFS in the different molecular subgroups.
• These results were found independently of the treatment received.
• They observed no beneficial effect of cetuximab on DFS or OS in left-sided tumors.