3613^ Background: The value of KRAS mutations as predictive markers of clinical benefit of anti-EGFR antibody therapy in patients with mCRC has been shown in randomized trials. Less is known of the influence of KRASmutations in patients with mCRC treated with VEGF signaling inhibitors and literature on the prognostic value of KRAS mutations in this setting is inconsistent. The Phase III HORIZON II (HZII) study evaluated the efficacy of cediranib 20 mg + FOLFOX (FF) or XELOX (X) vs placebo + FF or X in patients with mCRC; cediranib 20 mg met the co-primary endpoint of progression-free survival (PFS; HR=0.84) but not overall survival (OS; HR=0.94). A retrospective analysis of KRAS mutation status and correlation with PFS and OS in patients was performed to evaluate its prognostic and predictive value. Methods: Analysis of KRAS codon 12 and 13 mutations was performed at a central laboratory using a commercially available, allele-specific, ARMS-based polymerase chain reaction assay. Results: KRAS mutation status was determined in 489/860 patients (cediranib 20 mg arm, n=285/502; placebo arm, n=204/358); of these 489 patients, 42.3% had mutant KRAS and 57.7% were wild-type. Baseline characteristics were similar in the KRAS mutant, KRAS wild-type and KRAS status unknown groups. There was a trend towards improved PFS and OS in the KRAS wild-type subgroup compared with the KRAS mutant subgroup, which was independent of treatment arm (PFS: HR=0.85, 95% CI: 0.70,1.03, median 8.5 vs 8.3 months; OS: HR=0.71, 95% CI: 0.57,0.88, median 20.9 vs 16.9 months). There were no statistically significant differences in treatment effect between KRAS subgroups for the cediranib vs placebo arm (PFS: wild-type HR=0.78, mutant HR=0.82; OS: wild-type HR=0.92; mutant HR=1.01). Conclusions: This is the first reported analysis of KRAS mutation status in a randomized Phase III clinical study with a VEGFR-TKI. KRAS mutation status did not influence the PFS or OS treatment effect and therefore cannot be used as a predictive marker for outcome. These data show that KRAS codon 12 or 13 mutations have prognostic value in mCRC independent of treatment.