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

作者：Jordi Bruix, Jean‐Luc Raoul, Morris Sherman, Vincenzo Mazzaferro, Luigi Bolondi, Antonio Craxı̀, Peter R. Galle, Armando Santoro, Michel Beaugrand, Angelo Sangiovanni, Camillo Porta, Guido Gerken, Jorge A. Marrero, Andrea Nadel, Michael Shan, M. Moscovici, D. Voliotis, Josep M. Llovet · 发表于：Journal of Hepatology · 年份：2012 · DOI：10.1016/j.jhep.2012.06.014 · 被引用次数：825 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Hepatitis B Virus Studies、Liver Disease Diagnosis and Treatment

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 appreciab...