111P Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma compared to patients with advanced solid tumours

Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). In this comparative study, we aimed to compare incidence, clinical characteristics and outcomes of irLI between patients receiving ICIs for HCC versus other solid tumour indications. Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line Atezolizumab+Bevacizumab from AB-real study and a non-HCC cohort, including 459 patients treated with first-line ICI therapy from INVIDIa-2 multicentre study. IrLI was defined as treatment-related increase of transaminases levels after exclusion of alternative aetiologies of liver injury. Incidence of irLI was adjusted for the duration of treatment exposure. In HCC patients, incidence of any-grade irLI was 11.4% over a median treatment exposure of 4.4 months (95%CI 3.7-5.2), compared to 2.6% in INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95%CI 11.1-14.0). Exposure-adjusted incidence of any-grade irLI was 22.1 per 100-Patient-years (PY) in HCC patients and 2.1 per 100-PY in non-HCC patients (p<0.001), with median time to irLI of 1.4 in HCC and 4.7 months in non-HCC patients, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of HCC and in 75.0% of non-HCC patients (p<0.001) and irLI resolution was observed in 72.1% and 58.3%, respectively (p=0.362). In HCC patients, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. In both cohorts, no fatal irLI events occurred. Development of grade 1-2 irLI was associated with improved overall survival in HCC patients only (HR 0.53, 95%CI 0.29-0.96). Despite higher incidence and earlier onset in patients with HCC, IrLI is characterised by high rates of remission, low requirement for corticosteroid therapy and low risk of decompensation compared to other solid tumours. Hepatotoxicity leads to discontinuation in 7% of patients with HCC and does not negatively affect oncological outcomes.