• pMMR
• immunotherapy
• FOLFOXIRI
• metastatic colorectal cancer
• AtezoTRIBE

AtezoTRIBE phase II trial randomized 1:2 metastatic colorectal cancer (mCRC) patients unselected for mismatch repair (MMR) status to receive FOLFOXIRI/bevacizumab (control arm) or FOLFOXIRI/bevacizumab/atezolizumab (atezolizumab arm). It demonstrated that adding atezolizumab to first-line FOLFOXIRI/bevacizumab prolongs progression-free survival (PFS) of mCRC patients, with a modest benefit among proficient mismatch repair (pMMR) tumours. A deeper characterization of tumour immune microenvironment could help to identify patients who would derive maximal benefit from immune checkpoint inhibitors (ICIs) based treatment, particularly among pMMR, representing about 95% of mCRC patients.
DetermaIO is a gene expression signature measuring the expression of immune-related genes in tumour cells and its microenvironment. It is able to predict benefit from ICIs in triple negative breast cancer.
We investigated the predictive impact of DetermaIO in mCRC patients enrolled in AtezoTRIBE.
Gene expression was measured using RT-qPCR by DetermaIO™ on RNA purified from FFPE blocks of pre-treatment tumour samples (132/218 enrolled patients [61%]). IO score was calculated using the proprietary algorithm. Tumours were dichotomized as IO+ or IO- according to a pre-established cut-point (0.09), previously set in independent TNBC datasets, and as IOopt+ or IOopt- according to an exploratory optimized cut-point (IOopt).
DetermaIO was successfully determined in 122 (92%) cases, with 23 (27%) IO+. Patients with IO+ tumours achieved higher PFS benefit from the atezolizumab arm than those with IO- tumours (HR:0.39 versus 0.83, P for interaction=0.066). In pMMR tumours (N=110), a similar trend was observed (HR:0.47 versus 0.93, P for interaction=0.139). In the overall population (N=122), according to the computed IOopt cut-point (0.277), 16 (13%) tumours were IOopt+. IOopt+ derived higher PFS benefit from the atezolizumab arm than IOopt- ones (HR:0.10 versus 0.85, P for interaction=0.004). Similar results were observed in the pMMR subgroup.
In conclusion, DetermaIO may be useful to predict benefit from the addition of atezolizumab to first-line FOLFOXIRI/bevacizumab in mCRC patients. The exploratory IOopt cut-point should be validated in independent mCRC cohorts.