KRAS mutation, cancer recurrence, and patient survival in stage III colon cancer: Findings from CALGB 89803.
4037 Purpose: KRAS mutation in stage IV colorectal cancer predicts resistance to anti-EGFR targeted treatment (cetuximab or panitumumab). However, whether the presence of KRAS mutation independently predicts the survival of colon cancer patients remains uncertain. METHODS: We conducted a prospective observational study of 508 cases identified among 1264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) between April 1999 and May 2001 (CALGB 89803; Saltz et al. J Clin Oncol 2007). KRAS mutations were detected in 178 tumors (35%) by Pyrosequencing. Kaplan-Meier and Cox proportional hazard models were used to assess the significance of KRAS mutational status and adjusted for potential confounders including age, sex, tumor location, T stage, N stage, performance status, adjuvant chemotherapy arm and microsatellite instability (MSI) status. RESULTS: When compared to patients with wild-type KRAS, those with a mutation in KRAS did not experience any difference in disease-free (DFS), recurrence-free (RFS), or overall survival (OS) (log-rank P>0.56 for DFS, RFS, and OS). Five-year DFS was 62% for KRAS-mutated and 63% for KRAS-wild-type patients. Five-year RFS was 64% for KRAS-mutated and 66% for KRAS- wild-type patients. Five-year OS was 74% for KRAS-mutated and 73% for KRAS-wild-type patients. The effect of KRAS mutation on patient survival did not differ according to clinical features, chemotherapy arm or MSI status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. CONCLUSIONS: In this large clinical trial of chemotherapy in patients with stage III colon cancer, KRAS mutational status was not associated with any significant influence on disease-free or overall survival. No significant financial relationships to disclose.
Fuchs, C; Ogino, S; Meyerhardt, JA; Irahara, N; Niedzwiecki, D; Hollis, D; Saltz, LB; Mayer, RJ; Bertagnolli, MM
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