title: An updated meta-analysis of randomized controlled trials assessing the effect of sorafenib in advanced hepatocellular carcinoma.
abstract: BACKGROUND
  The efficacy of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC) remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of sorafenib for treating patients with advanced HCC.
  
  
  METHODS
  The PubMed, Embase, and Web of Science databases were searched. Eligible studies were randomized controlled trials (RCTs) that assessed sorafenib therapy in patients with advanced HCC. The outcomes included overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicities. Hazard ratio (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).
  
  
  RESULTS
  Seven RCTs, with a total of 3807 patients, were included in this meta-analysis. All patients received sorafenib alone, or with other chemotherapeutic regimens. Pooled estimates showed that sorafenib improved the OS (HR = 0.74, 95% CI: 0.61, 0.90; P = 0.002), or TTP outcomes (HR = 0.69, 95% CI: 0.55, 0.86; P = 0.001). Subgroup analysis revealed that sorafenib was more effective in the patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1-2 (HR = 0.77, 95% CI: 0.60, 1.0; P = 0.05), or macroscopic vascular invasion (MVI), and/or extrahepatic spread (EHS) (H  = 0.65, 95% CI: 0.46, 0.93; P = 0.02), in terms of OS. Patients who received sorafenib did not have a higher ORR (RR = 0.85, 95% CI: 0.65, 1.11; P = 0.10). In addition, there was a slight increase in toxicity in the sorafenib group.
  
  
  CONCLUSIONS
  Treatment with sorafenib significantly improved OS and TTP in patients with advanced HCC. Additional large-scale, well-designed RCTs are needed to evaluate the efficacy of sorafenib-based therapy in the treatment of advanced HCC.
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Jia
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Chaoliu
authors.initials: C
authors.lastname: Dai
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D061214:Patient Safety; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib