SO-28 FOLFOXIRI plus bevacizumab and atezolizumab as upfront treatment of unresectable mCRC patients: Updated and overall survival results of the phase II randomized AtezoTRIBE study

AtezoTRIBE (NCT03721653) is a phase II randomized trial in which unresectable mCRC pts were 1:2 to 1st-line FOLFOXIRI/bev [arm A] or FOLFOXIRI/bev/atezo B]. Adding atezo was safe and improved PFS (primary endpoint), with modest benefit also among pMMR tumors. Subgroup analyses suggest that TMB Immunoscore IC® (IS IC) -an IHC biomarker measuring CD8 PD-L1 cell densities their proximity- may identify tumors deriving from adding FOLFOXIRI/bev. The study had 85% power detect HR for (time randomization 1st PD death [PD1]) of 0.66 favor arm B 1-sided α error 0.10. Secondary endpoints included PFS2 on any treatment given after PD1 [PD2]), 2nd PD2), OS. MMR, TMB, IS IC correlated clinical outcome. 218 (arm A/B:73/145) enrolled. Main pts’ characteristics right-sided 44%/45%, RAS mut 71%/74%, BRAF 14%/8%, dMMR 7%/6%, high 10%/12%, 32%/32%. At median follow-up 37.0 mos, 175 (80%, A/B: 64/111) PD1, 150 (69%, 53/97) PD2, 118 (54%, 43/75) OS events collected. Out event, 135 (77%, A/B:50/85) received subsequent treatment; them, 121 43/78) PD2 event. In the intention-to-treat (ITT) population, significant advantage confirmed terms (HR:0.71, 80%CI 0.58-0.87, p=0.015), trend better outcome both (HR:0.85, 0.68-1.05, p=0.164) (HR:0.81, 80% CI 0.63-1.04, p=0.136). No differences observed between arms (HR:1.15, 0.90-1.48, p=0.228). Similar results reported group. ITT interactions MMR status (Pint 0.011), 0.008), 0.037) PFS. Only associated differential 0.065), bearing IC-high (HR:0.43, 95%CI 0.19-1.00), differently than those IC-low (HR:1.09, 0.65-1.83). group, 0.016 0.051, respectively) 0.043 0.063, respectively). Pts derived higher (HR:0.44, 0.19-1.03), 95% 0.67-1.97). and/or seem derive survival as upfront treatment. These findings deserve confirmation properly designed III trial.