Background: In the primary analysis of study 20100007, pmab + BSC significantly improved OS and PFS vs BSC in WT KRAS exon 2 mCRC and, in the first prospective phase 3 study, WT RAS (exons 2, 3, 4 of KRAS and NRAS) mCRC. We report the final analysis and evaluate BRAF status from study 20100007. Methods: Anti-EGFR naïve patients (pts) with WT KRAS exon 2 mCRC were randomized 1:1 to pmab + BSC or BSC. On-study crossover was prohibited. KRAS exon 2 and RAS status were assessed centrally. The primary endpoint was OS in WT KRAS exon 2 mCRC; secondary endpoints were OS in WT RAS mCRC and PFS and safety in both WT populations. Pts were followed for survival for ≥2 years after the last pt was randomized and a final analysis conducted. Results: 377 pts with WT KRAS exon 2 mCRC were enrolled; 84% had died at the final analysis (72% in the primary analysis). RAS ascertainment was 86%, BRAF was 84%. Pmab + BSC significantly improved OS and PFS vs BSC in WT KRAS exon 2 and WT RAS mCRC (See Table). No OS benefit was seen in mutant (MT) RAS mCRC with pmab (HR=1.09; 95% CI=0.56–2.16; P=0.80). BRAF mutations (descriptive analysis) were associated with poor prognosis (BSC; WT BRAF [n=142] vs MT BRAF [n=11], HR=0.33; 95% CI=0.16−0.65). No new toxicities were seen. Conclusions: Pmab significantly improved OS and PFS in chemorefractory WT KRAS exon 2 and WT RAS mCRC vs BSC, validating the importance of RAS testing at diagnosis. BRAF mutations appeared to be prognostic. Clinical trial information: NCT01412957

HR = hazard ratio