ANALYSIS AND EVALUATION OF CLINICAL AND PREDICTIVE BIOMARKERS OF RESPONSE TO IMMUNOTHERAPY IN THE ONCOLOGICAL FIELD

Background: Ipilimumab, Nivolumab and Pembrolizumab are the new immunotherapies today available, FDA approved both as first and second line treatment in different metastatic solid cancer. Despite their efficacy reported in literature is very promising, they still remain a therapy with a considerable outlay, both from an economic and safety point of view: the aim of our study is validate predictive biomarkers of treatment efficacy among hematological and faecal parameters normally used in clinical practice, in order to identify in advance which patients could really benefit from treatment. Methods: This is a three phase study which enrolled patients suffering from different metastatic solid cancer treated with immunotherapy. At the beginning our study was focused on Ipilimumab and, after the CARAMEL study we decided to explore also the new checkpoint inhibitors, Nivolumab and Pembrolizumab (CREAM and COFFEE study). We assessed before and regularly every 3 weeks a faecal sample and the full blood count with absolute WBC (aWBC), neutrophil count, eosinophil count, neutrophil/lymphocyte ratio (NLR), Platelets/lymphocyte ratio (PLR) and LDH serum levels. We evaluated the mutational BRAF status (among melanoma patients) and the number of metastatic sites involved before treatment (more or less than 3 sites). The cut-off values for our parameters were determined with time-dependent receiver operating characteristic (ROC) analysis. To identify prognostic and predictive biomarkers the above parameters have been correlated with Progression Free Survival (PFS) and Overall Survival (OS). As regards the CREAM study, we also evaluated the correlation between use of antibiotics within 30 days before the beginning of immunotherapy and our patients clinical outcome. Results: we found interesting correlation between clinical and pathological parameters and Conclusions: we well know our study presents many limits and, above all, we surey need a larger sample size to confirm our findings, but these data are very promising and, if confirmed, they really could help us to better manage the correct therapeutic sequence for treatment of metastatic patients.