Association of sorafenib plasma concentration with adverse events in a South Indian Hepatocellular carcinoma cohort

Introduction: Sorafenib exhibits substantial inter-individual variability in pharmacokinetic parameters in patients with hepatocellular carcinoma. Most real-world studies are from Western or Eastern Asian populations, with data correlating these factors being limited to the Indian cohort. Region-specific pharmacokinetic data are essential for supporting individualised dosing strategies. Aim This study aimed to characterise sorafenib trough concentrations in patients with HCC into defined exposure groups and determine the incidence and severity of sorafenib-associated adverse events. Method A prospective observational study was conducted in seventy-five HCC patients treated with sorafenib between 2021 and 2024. Trough concentrations of sorafenib and its metabolites were measured and stratified into defined exposure groups. Adverse events were graded, and their associations with trough concentrations and dose modifications were recorded. Results Wide inter-individual variability in trough concentrations was observed. The median sorafenib and its metabolite sorafenib-N-oxide concentrations increased across the exposure groups (p < 0.001). Sorafenib-related adverse events of grade 1–2 severity and laboratory abnormalities were observed. Conclusion Variability in sorafenib exposure among the South Indian population was demonstrated through this pharmacokinetic study, which highlights the need for therapeutic drug monitoring in optimising the sorafenib therapy in Indian patients.