Liver Cancer (Mar 2023)

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

  • Darren Jun Hao Tan,
  • Ansel Shao Pin Tang,
  • Wen Hui Lim,
  • Cheng Han Ng,
  • Benjamin Nah,
  • Clarissa Fu,
  • Jieling Xiao,
  • Benjamin Koh,
  • Phoebe Wen Lin Tay,
  • Eunice X Tan,
  • Margaret Teng,
  • Nicholas Syn,
  • Mark D Muthiah,
  • Nobuharu Tamaki,
  • Sung Won Lee,
  • Beom Kyung Kim,
  • Thomas Yau,
  • Arndt Vogel,
  • Rohit Loomba,
  • Daniel Q. Huang

DOI
https://doi.org/10.1159/000529824

Abstract

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Background: Emerging data suggest that outcomes for advanced hepatocellular carcinoma (HCC) treated with sorafenib may have improved over time. We aimed to provide robust, time-to-event estimates of survival outcomes for sorafenib in advanced HCC. Summary: 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). Key Messages: Survival outcomes for sorafenib in advanced HCC have improved over time. These data have important implications for clinical trial design.