Influence of KRAS mutations on clinical outcome in patients with curatively resected stage III colon cancer treated with adjuvant chemotherapy.

ABSTRACT

OBJECTIVE: To profile and correlate KRAS mutations with outcome in stage III colon cancer (CC) patients who underwent adjuvant chemotherapy following curative resection surgery. PATIENTS AND METHODS: In this retrospective study, eligible patients were those with resected stage III CC who underwent 6-months adjuvant chemotherapy, either with fluoropyrimidine monotherapy (FP) or with oxaliplatin-based regimens (O-FP). Disease-free survival (DFS) and overall survival (OS) were analyzed and computed using the Kaplan-Meier method and the log-rank test. RESULTS: The study population included 148 patients (n=65 FP and n=83 O-FP). We identified KRAS mutations in 41/148 (27%) patients, of which 18 (44%) received FP and 23 (56%) O-FP. Five-year DFS and OS were significantly higher in patients with KRAS wild-type vs. mutant [DFS 78 vs. 56%, HR 0.47 (95% CI 0.25; 0.87), p=0.01; OS 73 vs. 68%, HR 0.44 (95% CI 0.21; 0.88), p=0.01]. In patients treated with FP, the 5-year DFS and OS was significantly improved in the KRAS wild-type vs. mutant group, respectively [DFS 80 vs. 43%, HR 2.88 (95% CI 0.67; 3.76), p=0.014; OS 85 vs. 68%, HR 0.27 (95% CI 0.10; 0.73), p=0.005]. Conversely, 5-year DFS and OS were not statistically different for patients with KRAS wild-type vs. mutations treated with O-FP, respectively [DFS 78 vs. 65%, HR 1.59 (95% CI 0.67; 3.76), p=0.281; OS 80 vs. 75%, HR 0.73 (95% CI 0.55; 2.12), p=0.57)]. CONCLUSIONS: Our results suggest that curatively resected stage III CC patients exhibiting wild-type KRAS status might benefit from FP alone. Conversely, an oxaliplatin-containing regimen should be recommended in KRAS mutated patients.