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

C Antoniotti, A Boccaccino, R Seitz, M Giordano, A Catteau, D Rossini, Filomena Pietrantonio, Lisa Salvatore, K Mcgregor, F Bergamo, V Conca, S Leonetti, F Morano, G Papiani, E Tamburini, Maria Bensi, S Murgioni, Dt Ross, A Passardi, I BoquetTj Nielsen, J Galon, Mg Varga, Bl Schweitzer, C Cremolini

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Purpose: 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 inves-tigated the predictive impact of DetermaIO in mCRC.Experimental Design: Patients with mCRC unselected for MMR status were randomly assigned (1:2) to FOLFOXIRI plus bevacizumab (control arm) or the same regimen with atezolizu-mab (atezolizumab arm). qRT-PCR by DetermaIO was per-formed on RNA purified from pretreatment tumors of 132 (61%) of 218 enrolled patients. A binary result (IOpos vs. IOneg) adopting the preestablished DetermaIO cut-off point (0.09) was obtained, and an exploratory optimized cut-off point (IOOPT) was computed in the overall population and in pMMR subgroup (IOOPTpos vs. IOOPTneg).Results: DetermaIO was successfully determined in 122 (92%) cases, and 23 (27%) tumors were IOpos. IOpos tumors achieved higher PFS benefit from atezolizumab arm than IOneg (HR: 0.39 vs. 0.83; Pinteraction = 0.066). In pMMR tumors (N = 110), a similar trend was observed (HR: 0.47 vs. 0.93; Pinteraction = 0.139). In the overall population, with the computed IOOPT cut-off point (0.277), 16 (13%) tumors were IOOPTpos and they derived higher PFS benefit from atezolizumab than IOOPTneg (HR: 0.10 vs. 0.85, Pinteraction = 0.004). Similar results were found in the pMMR subgroup.Conclusions: DetermaIO may be useful to predict benefit of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in mCRC. The exploratory IOOPT cut-off point should be validated in independent mCRC cohorts.
Lingua originaleEnglish
pagine (da-a)2291-2298
Numero di pagine8
RivistaClinical Cancer Research
Volume29
DOI
Stato di pubblicazionePubblicato - 2023

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