TY - JOUR
T1 - An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer
AU - Antoniotti, Carlotta
AU - Boccaccino, Alessandra
AU - Seitz, Robert
AU - Giordano, Mirella
AU - Catteau, Aurelié
AU - Rossini, Daniele
AU - Pietrantonio, Filippo
AU - Pietrantonio, Filomena
AU - Salvatore, Lisa
AU - Mcgregor, Kimberly
AU - Bergamo, Francesca
AU - Conca, Veronica
AU - Leonetti, Simone
AU - Morano, Federica
AU - Papiani, Giorgio
AU - Tamburini, Emiliano
AU - Bensi, Maria
AU - Murgioni, Sabina
AU - Ross, Douglas Teller
AU - Passardi, Alessandro
AU - Boquet, Isabelle
AU - Nielsen, Tyler J.
AU - Galon, Jérôme
AU - Varga, Matthew Gordon
AU - Schweitzer, Brock L.
AU - Cremolini, Chiara
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - n/a
KW - n/a
UR - http://hdl.handle.net/10807/304448
U2 - 10.1158/1078-0432.CCR-22-3878
DO - 10.1158/1078-0432.CCR-22-3878
M3 - Article
SN - 1078-0432
VL - 29
SP - 2291
EP - 2298
JO - Clinical Cancer Research
JF - Clinical Cancer Research
ER -
