The albumin–bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development

Background: Drug development in hepatocellular carcinoma (HCC) is limited by disease heterogeneity, with hepatic reserve being a major source of variation in survival outcomes. The albumin–bilirubin (ALBI) grade is a validated index of liver function in patients with HCC. Aim: To test the accuracy of the ALBI grade in predicting post-sorafenib overall survival (PSOS) in patients who permanently discontinued treatment. Methods: From a prospectively maintained international database of 447 consecutive referrals, we derived 386 eligible patients treated with sorafenib within Barcelona Clinic Liver Cancer C stage (62%), 75% of whom were of Child class A at initiation. Clinical variables at sorafenib discontinuation were analysed for their impact on post-sorafenib overall survival using uni- and multivariable analyses. Results: Median post-sorafenib overall survival of the 386 eligible patients was 3.4 months and median sorafenib duration was 2.9 months, with commonest causes of cessation being disease progression (68%) and toxicity (24%). At discontinuation, 92 patients (24%) progressed to terminal stage, due to worsening Child class to C in 40 (10%). Median post-sorafenib overall survival in patients eligible for second-line therapies (n = 294) was 17.5, 7.5 and 1.9 months according respectively to ALBI grade 1, 2 and 3 (P < 0.001). Conclusions: The ALBI grade at sorafenib discontinuation identifies a subset of patients with prolonged stability of hepatic reserve and superior survival. This may allow improved patient selection for second-line therapies in advanced HCC.