Lenvatinib for the treatment of hepatocellular carcinoma - a real-world multicentre Australian cohort study

Abstract Introduction: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia.Methods:We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at eleven Australian tertiary centres. Baseline demographic data, tumour characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes.Results: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8- 9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p<0.01), new or worsening hypertension (HR 0.42, p<0.01), diarrhoea (HR 0.47, p=0.04) and more advanced BCLC stage (HR 2.50, p=0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p=0.04), the need for a dose reduction (HR 0.45, p<0.01) and age (HR 0.96, P <0.001). AEs occurred in 83.9% of patients with most being mild (71.6%).Conclusions:Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.