- 作者：Jordi Bruix ; Jean-Luc Raoul ; Morris Sherman ; Vincenzo Mazzaferro ; Luigi Bolondi ; Antonio Craxi ; Peter R. Galle ; Arm ; o Santoro ; Michel Beaugr ; Angelo Sangiovanni ; Camillo Porta ; Guido Gerken ; Jorge A. Marrero ; Andrea Nadel ; Michael Shan ; Marius Moscovici ; Dimitris Voliotis ; Josep M. Llovet
- 关键词：Hepatocellular carcinoma ; Sorafenib ; Subset analyses ; Overall survival ; Time to progression ; Disease control rate
- 刊名：Journal of Hepatology
- 出版年：2012
- 出版时间：October, 2012
- 年：2012
- 卷：57
- 期：4
- 页码：821-829
- 全文大小：934 K
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.