title: Geographic difference in survival outcome for advanced hepatocellular carcinoma: implications on future clinical trial design.
abstract: In clinical trials of systemic therapy for advanced hepatocellular carcinoma (HCC), Asian trials almost always reported poorer survival than non-Asian trials. This study sought to identify contributory factors for this geographic difference. A systematic review was done on randomized trials for unresectable HCC that used systemic therapy as an experimental arm and placebo or supportive care as control. Meta-analysis was performed with the consideration of fixed and random effects. Then, meta-regression was performed to identify predictors of patient survival in the control arm and the treatment effects (improvement in median survival). Fourteen trials (6 Asians, 8 non-Asians) were eligible for meta-analysis. The median survival of patients in the control arm, which indicated natural history of advanced HCC patients, was 3.57+/-1.88 months in Asian trials and 5.96+/-1.46 months in non-Asian trials (p=0.02). Independent predictors of better survival included non-Asian trials (p=0.0007), higher percentage of Child A cirrhosis (p=0.01) and hepatitis B (HBV)-related HCC (p=0.02). Sub-group analysis suggested that Asian trials tended to enroll patients with more advanced diseases. Independent predictors of better treatment effect included non-Asian trials, higher percentage of extra-hepatic metastasis, HBV-related HCC, and poorer trial quality. The quantitative estimation of the geographic difference can help design of future clinical trials of advanced HCC.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taiwan.
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Shen
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Cheng
authors.forename: Fu-Chang
authors.initials: FC
authors.lastname: Hu
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis