Effect of Gut Microbiome Composition on Atezolizumab Efficacy Among Patients With Colorectal Cancer

Translational Analysis of the AtezoTRIBE Study

At the 2023 World Congress on Gastrointestinal Cancers, Federica Marmorino, MD, University of Pisa, Italy, discusses the effect the gut microbiome composition may have on the efficacy of checkpoint inhibitors like atezolizumab for colorectal cancer.

Dr Marmorino stated that this research found for the first time that "species of bacteria may modulate the benefit from immune checkpoint inhibitors in proficient mismatch-repair metastatic colorectal cancer patients.”

Transcript:

Good morning. I am Federica Marmorino. I'm a medical oncologist and I work in Pisa, and I'm a researcher in University of Pisa. My clinical and research activity is focused on clinical and translational research on metastatic colorectal cancer. And the research that I will present at the 2023 World Congress on Gastrointestinal Cancers is focused on the identification of a biomarker of the benefit from immune checkpoint inhibitors in metastatic colorectal cancer patients.

We know that immune checkpoint inhibitors are the standard of treatment in deficient tumor patients, but these strategies are demonstrating disappointing results in proficient mismatch-repair metastatic colorectal cancer. We wanted to assess the potential predictor role of gut microbiome in metastatic colorectal cancer patients enrolled in AtezoTRIBE trial in order to identify a subgroup of these patients able to respond to immune checkpoint inhibitors.

The AtezoTRIBE trial is a phase 2, randomized trial, which compared 2 different strategies: the control arm received FOLFOXIRI plus bevacizumab and the experimental arm received FOLFOXIRI plus bevacizumab and atezolizumab, an anti-PDL1 agent. We collected baseline stool samples in patients enrolled in this trial and we analyzed by "shotgun" [untargeted] metagenomic analysis gut microbiome composition. Among patients with available baseline stool samples, we analyzed 163 cases.

The important results of our research showed for the first time that deficient tumor patients and proficient tumor patient have different baseline gut microbiome composition, and particularly deficient tumor ones have lower metagenomic diversity as compared with the proficient group with a statistical significant P-value.

The second important results of our research is in the group of proficient tumors, we identified a specific species of bacteria associated with progression-free survival according to the treatment arm. In particular, patients who have this specific species achieved longer progression-free survival when treated with experimental arm with atezolizumab, as compared with those treated in the control arm. No difference was reported when this specific bacterium is absent.

In conclusion, our results are the first prospective large trial in which species of bacteria may modulate the benefit from immune checkpoint inhibitors in proficient mismatch-repair metastatic colorectal cancer patients. These are preliminary results. These results need to be verified by using multivariate model, including other independent predictors of benefits, such as AtezoTRIBE Immunoscore-IC. But these results are important for future clinical direction because I can certify the response of the patients and perhaps can be used an oral supplement of these bacteria.

Thank you.

Source:

Marmorino F, Piccinno G, Rossini D, et al. Gut microbiome composition as predictor of the efficacy of adding atezolizumab to first-line FOLFOXIRI plus bevacizumab in metastatic colorectal cancer: a translational analysis of the AtezoTRIBE study. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-22