Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial

Jordi Bruix, Jean Luc Raoul, Morris Sherman, Vincenzo Mazzaferro, Luigi Bolondi, Antonio Craxi, Peter R. Galle, Armando Santoro, Michel Beaugrand, Angelo Sangiovanni, Camillo Porta, Guido Gerken, Jorge A. Marrero, Andrea Nadel, Michael Shan, Marius Moscovici, Dimitris Voliotis, Josep M. Llovet

Research output: Contribution to journalArticle

Abstract

Background & Aims: The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were randomized to receive either sorafenib 400 mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib. Methods: Five subgroup domains were assessed: disease etiology, tumor burden, performance status, tumor stage, and prior therapy. Overall survival (OS), time to progression (TTP), disease control rate (DCR), and safety were assessed for subgroups within each domain. Results: Subgroup analyses showed that sorafenib consistently improved median OS compared with placebo, as reflected by hazard ratios (HRs) of 0.50-0.85, similar to the complete cohort (HR = 0.69). Sorafenib also consistently improved median TTP (HR, 0.40-0.64), except in HBV-positive patients (HR, 1.03), and DCR. Results are limited by small patient numbers in some subsets. The most common grade 3/4 adverse events included diarrhea, hand-foot skin reaction, and fatigue; the incidence of which did not differ appreciably among subgroups. Conclusions: These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC, irrespective of disease etiology, baseline tumor burden, performance status, tumor stage, and prior therapy.

Original languageEnglish
Pages (from-to)821-829
Number of pages9
JournalJournal of Hepatology
Volume57
Issue number4
DOIs
Publication statusPublished - Oct 2012

Keywords

  • Disease control rate
  • Hepatocellular carcinoma
  • Overall survival
  • Sorafenib
  • Subset analyses
  • Time to progression

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial'. Together they form a unique fingerprint.

  • Cite this

    Bruix, J., Raoul, J. L., Sherman, M., Mazzaferro, V., Bolondi, L., Craxi, A., Galle, P. R., Santoro, A., Beaugrand, M., Sangiovanni, A., Porta, C., Gerken, G., Marrero, J. A., Nadel, A., Shan, M., Moscovici, M., Voliotis, D., & Llovet, J. M. (2012). Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Subanalyses of a phase III trial. Journal of Hepatology, 57(4), 821-829. https://doi.org/10.1016/j.jhep.2012.06.014