FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as initial treatment for metastatic colorectal cancer (TRIBE study): updated survival results and final molecular subgroups analyses.

Background: The phase III TRIBE study met its primary endpoint by demonstrating that first-line FOLFOXIRI plus bev significantly prolongs PFS, as compared to FOLFIRI plus bev (Loupakis et al, N Eng J Med 2014). At a median follow-up of 32.2 months a preliminary OS analysis indicated a borderline OS improvement with FOLFOXIRI plus bev (HR = 0.79, p = 0.054) with a consistent effect across RAS (KRAS and NRAS codons 12, 13, 61) and BRAFV600E molecular subgroups. Methods: 508 pts were randomized to either FOLFIRI plus bev (Arm A, N = 256) or FOLFOXIRI plus bev (Arm B, N = 252). On available samples from RAS and BRAF wild-type (wt) pts (N = 129), also KRAS and NRAS codons 59, 117 and 146 were analysed by means of Sequenom MassArray, identifying a new ???all wt??? population (N = 93). Results: At a median follow-up of 48.1 months, in the ITT population, updated median OS for Arm B vs Arm A was 29.8 vs 25.8 months (HR = 0.80, 95%CI, 0.65-0.98, p = 0.030). Estimated 5-years OS rate were: Arm B, 24.9% vs Arm A, 12.4%. Molecular results were informative for 357 pts (70.3%). All wt patients had longer OS as compared to RAS mutant (HR = 0.70, p = 0.006) and to BRAF mutant (HR = 0.24, p < 0.001). The benefit from FOLFOXIRI plus bev was consistent across all molecular subgroups (Table 1). All wt pts treated with FOLFOXIRI plus bev reported a median OS of 41.7 months as compared to 33.5 months in the FOLFIRI plus bev group (HR = 0.75, 95%CI, 0.45-1.24). Conclusions: FOLFOXIRI plus bev significantly improves survival of metastatic colorectal cancer pts and the OS advantage increases over time. Benefit from FOLFOXIRI plus bev is independent of RAS and BRAF mutational status. All wt pts have a better outcome independently from the treatment arm. Notable results with FOLFOXIRI plus bev are achieved in all wt pts. Arm A FOLFIRI+bev Arm B FOLFOXIRI+bev HR [95%CI] Arm A FOLFIRI+bev Arm B FOLFOXIRI+bev HR [95%CI] Median PFS (mos) Median PFS (mos) Median OS (mos) Median OS (mos) All wt (N = 93) 12.2 13.7 0.82 [0.53-1.26] 33.5 41.7 0.75 [0.45-1.24] RAS mut (N = 236) 9.5 12.0 0.82 [0.63-1.07] 23.9 27.3 0.95 [0.71-1.27] BRAF mut (N = 28) 5.5 7.5 0.56 [0.20-1.14] 10.8 19.1 0.60 [0.27-1.33