Abstract:
According to the Barcelona Clinic Liver Cancer (BCLC) staging system, only the advanced stage (stage C) hepatocellular carcinoma (HCC) patient is eligible for systemic treatments. In addition to tyrosine kinase inhibitors, multikinase inhibitors and anti-vascular-endothelial growth factor-2 (VEGF-R2), the systemic management of HCC has been revolutionized by the advent of immune checkpoint inhibitors (ICIs), a therapeutic class of monoclonal antibodies that blocks the immune checkpoints. Numerous studies, almost outside Africa and particularly Mali, on predictive biomarkers in various cancers treatment with ICIs were performed but predictive biomarkers ones in patients with advanced HCC under ICIs remain insufficient and are not multidimensional approaches to propose a patient-speci?c choice for ICIs treatment and even to develop simplified therapeutic algorithms and novel prognostic index for efficient HCC management. Our central hypothesis is that the global assessment of predictive biomarkers could help patient-speci?c choices for ICIs treatment by developing simplified therapeutic algorithms and novel prognostic index for efficient HCC management. To assess hematogical, biochemical, immunohistological, epigenetical, genetical and neoantigenic predictive biomarkers in Malian BCLC stage C HCC cohort treated with sorafenib or ICIs, we are going to conduct a national and multi-centre cohort study with prospective data collection during the study period between January 1, 2024 to December 31, 2026. The participants will be distributed in 1: 1 manner into experimental group/group A (ICIs mono or combination therapy with first or second line) and control group/group B (Sorafenib in first line). To detect a positive correlation between predictive biomarkers and clinical responses, irAEs and others outcomes, a cross-sectional analysis of data acquired during the follow-up between group A and group B will be done. This cohort study will make an important contribution to increase the knowledge on predictive biomarkers associated to therapeutic efficacy, immune-related adverse events (IrEAs) and others evolutionary outcomes in patient with HCC under ICIs. Our study will differ from previous studies by assessing globally the predictive biomarkers whose the well-conducted cross-sectional analysis could provide novel relevant predictive biomarkers, simplified therapeutic algorithm, and novel prognostic index development; and by holding in Africa particularly in Mali where predictive biomarkers especially in BCLC stage C HCC patient constitute almost a virgin ground.
