Survival Trends in Sorafenib for Advanced Hepatocellular Carcinoma: A Reconstructed Individual Patient Data Meta-analysis of Randomized Trials

Abstract

: In this systematic review and individual patient data meta-analysis of randomized-controlled trials (RCTs), we searched MEDLINE and Embase from inception till September 2022 for RCTs that provided data for overall survival (OS) and progression-free survival (PFS) for sorafenib monotherapy as first-line systemic therapy for advanced HCC. We performed a pooled analysis using reconstructed individual participant data from published Kaplan-Meier curves to obtain robust estimates for OS and PFS. Of 1,599 articles identified, 29 studies (5,525 patients) met the inclusion criteria. Overall, the median OS was 10.4 (95% CI 9.6 - 11.4) months. Median OS increased over time, from 9.8 (95% CI 8.8 - 10.7) months in studies before 2015, to 13.4 (95% CI 11.03 - 15.24) months in studies from 2015 onwards, p<0.001. OS did not differ by trial phase, geographical region, or study design. The overall median PFS was 4.4 (95% CI 3.9 - 4.8) months, but PFS did not improve over time. Sensitivity analysis of studies from 2015 and onwards to account for the introduction of direct-acting antivirals determined that hepatitis C virus was associated with reduced mortality (p<0.001). There was minimal heterogeneity in the estimates for OS (all I2= 33).