Efficacy and safety of sorafenib as first-line therapy of patients (pts) with advanced Child-Pugh B Hepatocellular Carcinoma (HCC): a systematic review and meta-analysis

Background: Sorafenib is the only agent that has demonstrated a survival benefit in pts with advanced HCC. However, the outcome of sorafenib therapy in pts with advanced HCC and Child-Pugh B liver function remains unresolved.Methods: A systematic review of electronic databases identified studies investigating the use of first-line sorafenib therapy in pts with advanced HCC and Child-Pugh A or B liver function. Meta-regression comprising a linear regression weighted by study sample size was conducted to explore the association between baseline factors and overall survival (OS). Differences between efficacy and safety and tolerability parameters were explored using a meta-analysis. For efficacy, the generic inverse variance approach was used to pool hazard ratios (HR) comparing Child-Pugh A to Child-Pugh B status. For safety and tolerability, the Mantel Haenszel method was used to pool data for the odds ratio for grade 3 or 4 adverse events (AEs) (Hand foot skin reaction, rash, diarrhoea, stomatitis, fatigue, hypertension, hyperbilirubinemia, ascites, encephalopathy). Results: Data were available from 32 studies (12 Asian) comprising 6,542 pts treated between Aug 2002 and Sep 2012. Among these were 4 RCTs and 28 cohort studies. The median age was 61 years and 83% were male. Hepatitis B and C status (when reported) was positive in 35% and 17% respectively. Child-Pugh status was available for 6,360 pts (97%) among whom 5,171 (81%) pts were classified as Child-Pugh A and 1,189 (19%) pts as Child-Pugh B (B7 in 17 studies [53%], no delineation in 15 studies [47%]). Estimated median OS on sorafenib therapy for the entire cohort was 7.6 months: 8.7 months in Child-Pugh A and 4.2 months in Child-Pugh B pts. Meta-regression showed significant positive association between OS and older age (p