Impact of K-ras status on FOLFOX and XELOX regimens efficacy in metastatic colorectal (mCRC) patients (pts).

Abstract

e14674 Background: Predictive value of K-ras status for the treatment with anti-EGFR monoclonal antibodies is well established. There is a lack of data about predictive significance of K-ras status for oxaliplatin-based chemotherapy (CT). We retrospectively studied prognostic and predictive significance of mutant K-ras in mCRC pts treated with FOLFOX or XELOX in 1st line CT. Methods: We analyzed data on 127 pts with mCRC, who were treated in our department during 2008-2011 with oxaliplatin-based regimens. K-ras status was determined by PCR analysis in 51/127 (40,1%) pts. Mutant K-ras was detected in 16/51 (31,3%) pts: 13/16 (81,3%) – codon 12, 3/16 (18,7%) – codon 13. mFOLFOX6 was administered in 21/51 (41,2%), XELOX – in 30/51 (58,8%) pts. No pts received anti-EGFR mAb in the 1-st line. Median follow-up was 9 months (range, 2 - 41). The mean number of courses was 9 and 5 in FOLFOX and XELOX groups, respectively. PFS was chosen as a primary end-point. Results: Median PFS was 7,5 months for all 127 pts, 8,4 months in pts with FOLFOX and 7,5 months in pts with XELOX. Median PFS in pts with wild type K-ras was 10,3 months and 6,5 months in pts with mutant K-ras (p=0,1, HR 1,7, 95%CI 0,9-3,4). Negative prognostic significance of mutant K-ras was seen in XELOX group (PFS, 10,9 vs 5,7 months, р= 0,002) but not in FOLFOX group (PFS, 7,7 vs 9,3 months, р= 0,48). In pts with wild type K-ras XELOX lead to longer PFS than FOLFOX regimen - 10,9 vs 7,5 months, respectively (р=0,09, HR 0,52, 95%CI 0,23-1,14). And vice versa, in pts with mutant K-ras FOLFOX was more active than XELOX – median PFS was 9,3 vs 5,7 months, respectively (р=0,009, HR 0,3, 95%CI 0,05-0,64). Conclusions: Our findings probably suggest that K-ras status influences the efficacy of FOLFOX and XELOX regimens in mCRC pts. These data need to be confirmed in larger series of pts.