In this interview, I will present the results of a translational analysis of the Italian drug study. AtezoTRIBE is a phase two comparative randomized study, which metastatic colorectal cancer patients were randomized to receive a first line for FOLFOXIRI plus bevacizumab with or without atezolizumab the study method, the primary endpoint showing that the addition of atezolizumab FOLFOXIRI plus Bev prolongs progression-free survival in the overall population, a modest clinical benefit is reported or among patients with proficient is match repair tumors. This results also lead to the search for predictors of benefit from this therapeutic approach.
In this perspective that (inaudible) is an immune related gene expression, signature showing a correlation with the efficacy of immune checkpoint blockade in different solid tumors. However, nowadays, whether these gene expression signature. Could predict the benefit from an IC-based therapeutic approach. Metastatic colorectal cancer has never been investigated.
We performed (inaudible) expression analysis onto more tissues from patients enrolled in the AtezoTRIBE study. We did the primary aim of investigating the relative benefit from the addition. Plus be according to the determine, you start by adopting a predefining cut point. A secondary analysis was exploratory conducted to define and optimize a yield point in our study court.
In order to identify patients deriving the maximum benefit from the experimental strategy. RNA was obtained from 142 cases. And under one PC analysis by using the determin targeted panel testing 20 S genes, it incorporates both tumor and immune microenvironment. Gene expression reflecting the presence of infiltrating inflammatory cells versus differentiated the strong microenvironment.
For each case in IO score was calculated according to the slab established upon cancer, U algorithm, and a pretty define cut point of 0.09 was applied to atomized tumors as higher, positive, or higher negative for the exploratory analysis. We completed and optimized a point in both the overall population and in the profession, (inaudible) repair subgroup by maximize the longer statistics for comparing 2 groups.
The IO status was assessed in 122 cases. And by adopting the predefining AAT point of 0.09, 27% of tumors were classified as higher positive. Between high, positive, and IO negative tumors, no differences in terms of baseline characteristics are reported, and no overlap among high positivity and other immune-related biomarkers, such as deficiency is measure repair and high TMB.
It reported no differences in terms of outcome in particular, in terms of progression-free survival is reported, between higher, positive, and are negative tumors in both the overall population and also in the profession match repair subgroup. An interaction is observed between the treatment effect and the IO status.
In fact, a higher benefit from the addition atezolizumab plus Bev is reported among patients with higher positive IO, positive tumors. Then among those with higher negative tumors. and similar results are, observed in the proficient (inaudible) per population. for the secondary analysis in the overall population and optimize a yield point of 0.27 was competed in this case.
In this way, we classified as a HER2 positive, about 13% of tumors, and they had a better outcome in terms of progression for survival as compared to the higher negative ones. And angenous treatment effect is reported. According to the determine your status. In fact, a significant higher benefit from the additional FOLFOXIRI plus Bev is reported among patients with higher, positive than among the dose, even then among those with higher negative tumors.
We replicated the same analysis in the proficient (inaudible) repair sub-population. And in this case, the optimizer yogurt point was complicated. 0.304. In this way, 11% of tumors were classified, has higher positive. And also, in this case, they had a better outcome in terms of, progression for survival and they derived, higher, higher benefit from the addition of tib Toi plus.
Our results also support the hypothesis that a deeper characterization of tumor macro environment could allow identify patients achieving benefit from an icy-based therapeutic approach in metastatic colorectal cancer. Investigated are your signal to using both the pre-defined and the optimized cutpoint maybe help full I predictive.
I predicting the benefit from the addition of a plus in meta Al cancer with how weak signal or so within patients with proficient (inaudible) per tumors, and, finally our results support. This (inaudible) as an immuno classifier worthy of further investigation in independent course of patients with metastatic colorectal cancer.
Carlotta Antoniotti, MD, from the Department of oncology, transplants and new technologies at Pisan University Hospital. In this video, she speaks about the ASCO 2022 Abstract – An immune-related gene expression profile to predict the efficacy of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in metastatic colorectal cancer: A translational analysis of the phase II randomized AtezoTRIBE study.
Synopsis:
This is a prospective, open-label, multicentric phase II randomized in a 1:2 ratio trial in which patients with initially unresectable and previously untreated mCRC will receive induction treatment with FOLFOXIRI plus bev for up to 8 cycles, followed by maintenance treatment with 5-FU/LV plus bev until disease progression, unacceptable toxicity, or patient refusal (arm A) versus FOLFOXIRI plus bev plus atezolizumab for up to 8 cycles, followed (arm B). If disease development does not occur during induction, the treating physician may reintroduce the same induction treatment (up to 8 cycles) based on the randomization arm, followed by maintenance until disease progression, intolerable toxicity, or patient refusal.
The third and subsequent lines of treatment will be determined by the investigators.