Sorafenib as first-line therapy in patients with advanced Child-Pugh B Hepatocellular Carcinoma – a meta-analysis

Background: Sorafenib has demonstrated survival benefit in first-line treatment of advanced hepatocellular carcinoma (HCC); utility of sorafenib in patients with advanced HCC and Child-Pugh B (CP-B) liver function remains a subject of debate. Methods: A systematic review identified studies using first-line sorafenib in patients with advanced HCC and CP-A/B liver function. Meta-regression analysis comprising linear regression was conducted to explore association between baseline factors and overall survival (OS). Differences between efficacy/safety and tolerability parameters were explored using meta-analysis. Results: 30 studies (12 Asian) comprising 8,678 patients (Aug 2002-Sep 2012) were included (4 randomised-controlled-trials, 26 cohort-studies). Median age; 61-years; 83%-male. Hepatitis B/C status positive in 35%/22% respectively. CP status available for 8,577 patients (99%); 79% CP-A, 19% CP-B. Median OS on sorafenib for entire cohort: 7.2 months; 8.8 months in CP-A, 4.6 months in CP-B. Multivariable meta-regression analysis showed significant negative association between OS and proportion of patients with ECOG-PS-2 (P=0.04) and CP-B liver function (P=0.001). Among 4 studies reporting multivariable comparison of CP status, CP-B was associated with significantly worse OS (P<0.001). There were no differences in response rate to sorafenib between patients with CP-A (4.6%) or CP-B liver function (4.2%). Safety and tolerability were similar; 35% of patients with CP-A/B liver function developed grade 3/4 AEs (P=0.7). Meta-regression analysis showed similar rates of treatment discontinuation without progression (P=0.31) and treatment-related death (P=0.94) in patients with CP-B liver function. Conclusion: CP-B liver function (versus CP-A) is associated with worse OS (but similar response rate, safety and tolerability of first-line sorafenib; unlikely to be clinically meaningful).