Sorafenib is associated with a reduced rate of tumour growth and liver function deterioration in HCV-induced hepatocellular carcinoma

Research output: Contribution to journalArticlepeer-review

Authors

  • Ruwanthi Kolamunnage-Dona
  • Harry Potts
  • Edward H Williams
  • James Tanner
  • Tobias Janowitz
  • Matthew Hoare
  • Philip Johnson

Colleges, School and Institutes

External organisations

  • University of Liverpool
  • Queen Elizabeth Hospital Birmingham
  • University of Cambridge
  • Cold Spring Harbor Laboratory
  • Northwell Health Cancer Institute

Abstract

BACKGROUND & AIMS: Sorafenib has been the standard of care for patients with advanced hepatocellular carcinoma and although immunotherapeutic approaches are now challenging this position, it retains an advantage in HCV-seropositive patients. We aimed to quantify the rate of tumour progression in patients receiving sorafenib and relate this figure to survival, both overall, and according to viral status.

METHODS: Using serial data from an international clinical trial we applied a joint model to combine survival and progression over time in order to estimate the rate of tumour growth as assessed by tumour burden and serum alpha-fetoprotein, and the impact of treatment on liver function.

RESULTS: High tumour burden at baseline was associated with an increased risk of death. In patients still alive at the end of the study, the progression in relation to tumour burden was very low compared to those who died within the study. Overall, the change in mean tumour burden was 0.12 mm per day or an absolute growth rate of 3.6 mm/month. Median doubling time was 665 days. For those who progressed above 0.12 mm per day or the 12% rate, median survival was 234 days compared to 384 days if the rate was below 12%. Tumour growth rate and serum alpha-fetoprotein rise were significantly lower in those who were HCV seropositive as was the rate of decline in liver function. These results were replicated in 2 independent patient groups.

CONCLUSION: Our analysis suggests that sorafenib treatment is associated with improved survival in patients with advanced hepatocellular carcinoma mainly by decreasing the rate of tumour growth and liver function deterioration among patients with HCV infection.

LAY SUMMARY: Among patients receiving sorafenib for advanced hepatocellular carcinoma the rate of tumour growth (as assessed by changes in tumour size and the biomarker alpha-fetoprotein) and the deterioration of liver function is less in those who have the hepatitis C virus, than in those who do not.

Bibliographic note

Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Details

Original languageEnglish
JournalJournal of Hepatology
Early online date27 May 2021
Publication statusE-pub ahead of print - 27 May 2021

Keywords

  • hepatocellular carcinoma, hepatitis C virus, tumour progression rate, sorafenib, joint modelling

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