Original Research| Volume 153, P16-26, August 2021

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


      • 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.



      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.

      Patients and methods

      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.


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