Association of KRAS mutation with worse recurrence-free survival and site of metastatic progression after resection of hepatic colorectal metastases.

Abstract

3609 Background: There are conflicting results regarding the influence of KRAS mutation status and outcome in patients (pts) with colorectal cancer. A recent report suggested worse outcome in KRAS mutated (MUT) pts who underwent resection of hepatic metastases (Karagkounis et al, ASCO 2012). Methods: Recurrence patterns and survival were evaluated in 169 patients who had undergone resection of liver metastases, then received adjuvant hepatic arterial infusion and systemic chemotherapy, and for whom KRAS data were available. Kaplan-Meier methods were used to estimate recurrence free survival (RFS) and overall survival (OS). Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adjuvant therapy to bone, brain, lung and liver metastases separately. Mutations in KRAS (codons 12, 13) were detected using the iPLEX assay (Sequenom, Inc). Results: Median follow-up for the entire cohort was 38.8 months. 118 were KRAS wildtype (WT), and 51 were KRAS MUT (45 G12, 5 G13, 1 K117N). The 3 year RFS was 48% [95%CI: 37-58%] for KRAS WT pts and 30% [15-44%] for MUT pts (p<0.01). OS at 3 years was 96% [88-98%] for KRAS WT and 80% [61-90%] for MUT pts (p=0.08). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in Table 1. The cumulative incidence of metastases to bone at 2 years was 0% and 13.7% in KRAS WT versus MUT pts (p<0.01), to brain 0% versus 4.6% for KRAS WT versus MUT (p=0.05), and to lung 27% versus 47.5% in KRAS WT versus MUT pts (p<0.01). Conclusions: In pts who have had liver resection followed by adjuvant therapy, those with KRAS MUT have a worse RFS and seemingly worse OS than those who are KRAS WT. Also, patients with KRAS MUT appear more likely to develop bone, brain, and lung metastases. Further investigation of a larger number of patients is warranted. [Table: see text]