Exploring clinical and gene expression markers of benefit from FOLFOXIRI/bevacizumab in patients with BRAF-mutated metastatic colorectal cancer: Subgroup analyses of the TRIBE2 study.

Recent data from the TRIBE2 study have failed to suggest a higher magnitude of benefit from upfront FOLFOXIRI/bevacizumab in patients with BRAF -mutant metastatic colorectal cancer (mCRC) as previously reported in the TRIBE study. Clinical characteristics and gene expression signatures of patients with BRAF-mutant mCRC enrolled in the TRIBE2 study were evaluated with the aim of understanding that patients may derive benefit from the intensification of the upfront chemotherapy. Of 46 BRAF-mutant tumour samples analysed, 24 (52%) and 22 (48%) were classified as BM1 and BM2, respectively, and 27 (59%) and 19 (41%) were assigned to ligand-independent (LI) and ligand-dependent (LD) Wnt pathway subgroups, respectively. No prognostic impact was shown for both BM1/BM2 and LI/LD subtypes. No interaction was evident between BM1/BM2 or LI/LD signatures and the benefit provided by FOLFOXIRI/bevacizumab. Significant interaction effect was evident in terms of progression-free survival between treatment arm and primary tumour sidedness (P = 0.05) and Eastern Cooperative Oncology Group performance status (ECOG-PS; P < 0.001). Gene expression analysis failed to identify patients with BRAF-mutant mCRC candidate to upfront FOLFOXIRI/bevacizumab. ECOG-PS >0 and left-sidedness seem associated with no benefit from the intensified treatment. • A restricted panel of 44 genes discerns BM1/BM2 subtypes of BRAF mut mCRC. • AXIN2 expression distinguishes LI versus LD Wnt pathway activation of BRAF mut mCRC. • No prognostic impact was shown for both BM1/BM2 and LI/LD subtypes. • No predictive effect of both BM1/BM2 and LI/LD subtypes was shown for FOLFOXIRI/bev. • ECOG-PS >0 and left-sidedness seem associated with no benefit from FOLFOXIRI/bev. [ABSTRACT FROM AUTHOR]