TY - JOUR
T1 - Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma
T2 - Subanalyses of a phase III trial
AU - Bruix, Jordi
AU - Raoul, Jean Luc
AU - Sherman, Morris
AU - Mazzaferro, Vincenzo
AU - Bolondi, Luigi
AU - Craxi, Antonio
AU - Galle, Peter R.
AU - Santoro, Armando
AU - Beaugrand, Michel
AU - Sangiovanni, Angelo
AU - Porta, Camillo
AU - Gerken, Guido
AU - Marrero, Jorge A.
AU - Nadel, Andrea
AU - Shan, Michael
AU - Moscovici, Marius
AU - Voliotis, Dimitris
AU - Llovet, Josep M.
N1 - Funding Information:
The study was supported by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. CIBERehd is funded by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación . Dr. J. Bruix has a Grant from the Instituto de Salud Carlos III ( PI 08/0146 ). Dr. J. M. Llovet has Grants from National Institutes of Health—NIDDK 1R01DK076986-01, FP7-2010-Health European Commission Grant HEPTROMIC: 259744–2; National Institute of Health (Spain) Grant I+D Program (SAF-2007-61898); and Samuel Waxman Cancer Research Foundation.
Funding Information:
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.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Disease control rate
KW - Hepatocellular carcinoma
KW - Overall survival
KW - Sorafenib
KW - Subset analyses
KW - Time to progression
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U2 - 10.1016/j.jhep.2012.06.014
DO - 10.1016/j.jhep.2012.06.014
M3 - Article
C2 - 22727733
AN - SCOPUS:84866391058
SN - 0168-8278
VL - 57
SP - 821
EP - 829
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -