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

Aliment Pharmacol Ther. 2017 Mar;45(5):714-722. doi: 10.1111/apt.13904. Epub 2017 Jan 24.

Abstract

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Albumins / metabolism
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Bilirubin / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Databases, Factual
  • Disease Progression
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Patient Selection
  • Phenylurea Compounds / administration & dosage*
  • Prospective Studies
  • Sorafenib

Substances

  • Albumins
  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • Bilirubin