title: Impact of Viral Status on Survival in Patients Receiving Sorafenib for Advanced Hepatocellular Cancer: A Meta-Analysis of Randomized Phase III Trials.
abstract: Purpose Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log [hazard ratio], -0.27; 95% CI, -0.46 to -0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for "other" treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran's Q statistic. Conclusion There is consistent evidence that the effect of sorafenib on OS is dependent on patients' hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV.
authors.affiliation: Richard Jackson and Eftychia-Eirini Psarelli, Liverpool Cancer Trials Unit; Sarah Berhane and Philip Johnson, University of Liverpool, Liverpool; Harun Khan, Imperial College London, London; and Philip Johnson, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Jackson
authors.affiliation: Richard Jackson and Eftychia-Eirini Psarelli, Liverpool Cancer Trials Unit; Sarah Berhane and Philip Johnson, University of Liverpool, Liverpool; Harun Khan, Imperial College London, London; and Philip Johnson, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom.
authors.forename: Eftychia-Eirini
authors.initials: EE
authors.lastname: Psarelli
authors.affiliation: Richard Jackson and Eftychia-Eirini Psarelli, Liverpool Cancer Trials Unit; Sarah Berhane and Philip Johnson, University of Liverpool, Liverpool; Harun Khan, Imperial College London, London; and Philip Johnson, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Berhane
authors.affiliation: Richard Jackson and Eftychia-Eirini Psarelli, Liverpool Cancer Trials Unit; Sarah Berhane and Philip Johnson, University of Liverpool, Liverpool; Harun Khan, Imperial College London, London; and Philip Johnson, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom.
authors.forename: Harun
authors.initials: H
authors.lastname: Khan
authors.affiliation: Richard Jackson and Eftychia-Eirini Psarelli, Liverpool Cancer Trials Unit; Sarah Berhane and Philip Johnson, University of Liverpool, Liverpool; Harun Khan, Imperial College London, London; and Philip Johnson, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Johnson
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib