Background: Previously, extended RAS analysis from this study showed a trend toward improvements in HR on OS and PFS with pmab + FOLFIRI vs FOLFIRI in WT RAS group vs WT KRAS exon 2 group. Here we report updated RAS data and new analysis by BRAF status. Methods: The primary objective was to assess the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS based on RAS/BRAF mutation status in the primary analysis population. Bidirectional Sanger sequencing was used to detect mutations in KRAS exons 3, 4 and NRAS exons 2, 3, 4, and BRAF exon 15 in patients (pts) with known WT KRAS exon 2 mCRC. Results: Overall RAS/BRAF ascertainment rate was 85% (n=1014/1186). 18% of WT KRAS exon 2 pts harbored additional RAS mutations (n=107/597). The incidence of BRAF mutations was 8.3% (45/541). Efficacy is shown (table). Tx HR for pts with WT RAS was 0.81 (95% CI: 0.63, 1.03; P=0.08) for OS and 0.70 (95% CI: 0.54, 0.91; P=0.007) for PFS. Conclusions: Improvements continued to be observed in the tx effect of pmab + FOLFIRI vs FOLFIRI on OS and PFS in WT RAS group vs WT KRAS exon 2 group in this update. Pts with MT RAS mCRC are unlikely to benefit by the addition of pmab to FOLFIRI, similar to pts with MT KRAS exon 2 mCRC. BRAF mutations appear to be associated with reduced OS among pts without RAS mutations regardless of tx arm. These findings support RAS testing to determine potentially appropriate pts with mCRC for pmab tx. Clinical trial information: NCT00339183.

^a WT in KRAS and NRASexons 2, 3, and 4.^b MT in any KRAS or NRAS exon 2, 3, or 4. ^c WT for all RAS and BRAF exons. ^d WT for all RAS and MT BRAF exons.