Subgroup Analyses In Ras Mutant, Braf Mutant And All-Wt Mcrc Pts Treated With Folfoxiri Plus Bevacizumab (Bev) Or Folfiri Plus Bev In The Tribe Study.

3519 Background: Phase III TRIBE trial demonstrated that first-line FOLFOXIRI plus bev improved PFS and RECIST response and, at adjusted analyses, OS as compared to FOLFIRI plus bev. The prognostic and/or predictive effect to anti-EGFRs of RAS and BRAFmutation is well established. We conducted this post-hoc analysis in the TRIBE study in order to describe the predictive and prognostic effect of each molecular cathegory. Methods: Mutational analyses were centralized at the Coordinating Center. Mutations within KRAS and NRAS codon 12, 13 and 61 and BRAF codon 600 were analyzed by means of pyrosequencing in tumoral DNA extracted from primaries or metastases. Pts not bearing RAS or BRAFmutations were defined as “all wt”. Results: Molecular results are available for 375 out of 508 randomized pts (73.8%). KRAS, NRAS and BRAF were found mutated (mut) in 198 (52.8%), 20 (5.3%) and 28 (7.5%) cases, respectively. All wt pts were 129 (34.4%). Predictive analyses: see table. No significant interaction between RAS or BRAF status and treatment effect was reported in PFS or OS. All wt pts treated with upfront FOLFOXIRI plus bev achieved median PFS and OS of 13.3 and 41.7 mos, respectively. Prognostic analyses: as compared to all wt pts, BRAF mut had significantly shorter PFS (HR: 2.29 [1.49-3.52], p=0.0002) and OS (HR: 3.31 [2.03-5.39], p<0.0001) while for RASmut no difference in PFS was detected (HR: 1.15 [0.91-1.45], p=0.256), but OS was significantly shorter (HR: 1.48 [1.09-2.00], p=0.012). Conclusions: Benefit from FOLFOXIRI plus bev was independent of RAS and BRAF mutational status, with a trend toward a larger benefit in BRAF mut limited by small subgroup size. All wt pts treated with FOLFOXIRI plus bev achieved impressive PFS and OS results. Independently from the treatment received RAS or BRAFmut pts had shorter long-term survival. Clinical trial information: NCT00719797. FOLFIRI+bev FOLFOXIRI+bev HR (95%CI) mPFS mOS mPFS mOS PFS OS All wt (N=129) 11.3 34.4 13.3 41.7 0.77 (0.52-1.12) 0.84 (0.51-1.38) RAS mut (N=218) 9.5 23.1 12.0 28.6 0.82 (0.62-1.09) 0.86 (0.61-1.23) BRAF mut (N=28) 5.5 10.8 7.5 19.1 0.56 (0.20-1.14) 0.55 (0.24-1.23)