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Clinical Trial
. 2012 Oct;57(4):821-9.
doi: 10.1016/j.jhep.2012.06.014. Epub 2012 Jun 19.

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

Jordi Bruix  1 , 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
Affiliations
Clinical Trial

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

Jordi Bruix et al. J Hepatol. 2012 Oct.

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 400mg 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.

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Conflict of interest statement

Conflict of interest

Jordi Bruix has received honoraria and research funding from Bayer HealthCare Pharmaceuticals and consulting fees from Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Biocompatibles, Bristol-Myers Squibb, Glaxo, Kowa, Novartis, and ArQule; Jean-Luc Raoul has received consulting fees from Bayer HealthCare Pharmaceuticals and Biocompatibles and lecture fees from Bayer HealthCare Pharmaceuticals; Vincenzo Mazzaferro has received consulting fees from Bayer HealthCare Pharmaceuticals; Luigi Bolondi has received consulting and lecture fees from Bayer HealthCare Pharmaceuticals; Peter R. Galle has received consulting and lecture fees from Bayer HealthCare Pharmaceuticals; Armando Santoro has received consulting fees from Bayer HealthCare Pharmaceuticals; Camillo Porta has received consulting and lecture fees and research Grants from Bayer HealthCare Pharmaceuticals; Jorge A. Marrero has received consulting fees from Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals; Andrea Nadel, Michael Shan, and Dimitris Voliotis are employees of Bayer HealthCare Pharmaceuticals; Marius Moscovici is an employee of Bayer Schering Pharma; Josep M. Llovet has received consulting fees from Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals and honoraria and research funding from Bayer HealthCare Pharmaceuticals. No other potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.. Relationship between etiology of HCC and survival outcomes in patients enrolled in the SHARP trial.
Overall survival (OS) in patients with HCC due to (A) hepatitis C virus (HCV) infection, (C) hepatitis B virus (HBV) infection, and (E) chronic alcohol consumption. Time to progression (TTP) in patients with HCC due to (B) HCV infection, (D) HBV infection, and (F) chronic alcohol consumption.
Fig. 2.
Fig. 2.. Relationship between Barcelona Clínic Liver Cancer (BCLC) stage and survival outcomes in patients enrolled in the SHARP trial.
Overall survival (OS) in patients with (A) BCLC B and (C) BCLC C stage. Time to progression (TTP) in patients with (B) BCLC B and (D) BCLC C stage.
Fig. 3.
Fig. 3.. Relationship between prior treatment and survival outcomes in patients enrolled in the SHARP trial.
Overall survival (OS) in patients with (A) prior curative treatment (resection/local ablation, percutaneous ethanol injection, or radiofrequency ablation) and (C) prior transarterial chemoembolization (TACE). Time to progression (TTP) in patients with (B) prior curative treatment and (D) prior TACE.
Fig. 4.
Fig. 4.. Summary of efficacy and safety outcomes for subgroups of patients enrolled in the SHARP trial.
(A) Overall survival, (B) time to progression, (C) disease control rate, and (D) frequency of grade 3/4 adverse events among subgroups of patients with advanced HCC randomized to sorafenib or placebo.
See this image and copyright information in PMC

References

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