Entry Detail
| General information | |
| Database: | DB00871 |
| Objective: | The Sorafenib Hepatocellular Carcinoma (hepatocellular carcinoma) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced hepatocellular carcinoma. In this trial, 602 patients with wellpreserved liver function (>95% ChildPugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because hepatocellular carcinoma 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. |
| Authors: | Bruix J, et al |
| Title: | Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. |
| Journal: | J Hepatol. |
| Year: | 2012 |
| PMID: | 22727733 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | liver cancer |
| Cancer Subtype: | hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | subanalyses of a phase III trial |
| Key Patients Feature: | patients with wellpreserved liver function (>95% ChildPugh A) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sorafenib versus placebo |
| Treatment Info: | Five subgroup domains were assessed: disease etiology, tumor burden, performance status, tumor stage, and prior therapy |
| Primary End Point: | Overall survival (OS), time to progression (TTP), disease control rate (DCR), and safety were assessed for subgroups within each domain |
| Secondary End Point: | NA |
| Patients Number: | 602 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 44.2% vs. 29.6% in HCVinfected patients. 34.4% vs. 32.1% in HBVpositive patients. |
| Median Time to Progression: | 14.0 vs. 7.4 months in HCVinfected patients. 34.4% vs. 32.1% in HBVpositive patients. |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 14.0 vs. 7.4 months in HCVinfected patients. 9.7 vs. 6.1 months in HBVpositive patients. |
| Adverse Event(agent arm): | The incidence of adverse events (AEs) was similar across all subgroups. The most frequently reported drugrelated treatmentemergent AEs in patients receiving sorafenib were diarrhea, fatigue, anorexia, and handfoot skin reaction (HFSR). The incidence of drug related AEs of any severity in the sorafenib and placebo subgroups were 71.9-84.9% and 43.2-60.7%, respectively, and the incidences of drug related SAEs were 9.4-14.6% and 5.0-25%, respectively. |
| Conclusions: | These exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced hepatocellular carcinoma, irrespective of disease etiology, baseline tumor burden, performance status, tumor stage, and prior therapy. |