Data from An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer

<div>AbstractPurpose:<p>AtezoTRIBE phase II randomized study demonstrated that adding atezolizumab to first-line FOLFOXIRI (5-fluorouracil, oxaliplatin, irinotecan) plus bevacizumab prolongs progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC), with a modest benefit among proficient mismatch repair (pMMR). DetermaIO is an immune-related 27-gene expression signature able to predict benefit from immune checkpoint inhibition in triple-negative breast cancer. In this analysis of AtezoTRIBE, we investigated the predictive impact of DetermaIO in mCRC.</p>Experimental Design:<p>Patients with mCRC unselected for MMR status were randomly assigned (1:2) to FOLFOXIRI plus bevacizumab (control arm) or the same regimen with atezolizumab (atezolizumab arm). qRT-PCR by DetermaIO was performed on RNA purified from pretreatment tumors of 132 (61%) of 218 enrolled patients. A binary result (IO^pos vs. IO^neg) adopting the preestablished DetermaIO cut-off point (0.09) was obtained, and an exploratory optimized cut-off point (IO^OPT) was computed in the overall population and in pMMR subgroup (IO^OPTpos vs. IO^OPTneg).</p>Results:<p>DetermaIO was successfully determined in 122 (92%) cases, and 23 (27%) tumors were IO^pos. IO^pos tumors achieved higher PFS benefit from atezolizumab arm than IO^neg (HR: 0.39 vs. 0.83; <i>P</i>_interaction = 0.066). In pMMR tumors (<i>N</i> = 110), a similar trend was observed (HR: 0.47 vs. 0.93; <i>P</i>_interaction = 0.139). In the overall population, with the computed IO^OPT cut-off point (0.277), 16 (13%) tumors were IO^OPTpos and they derived higher PFS benefit from atezolizumab than IO^OPTneg (HR: 0.10 vs. 0.85, <i>P</i>_interaction = 0.004). Similar results were found in the pMMR subgroup.</p>Conclusions:<p>DetermaIO may be useful to predict benefit of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in mCRC. The exploratory IO^OPT cut-off point should be validated in independent mCRC cohorts.</p></div>