Presentation (CTI)

OBJECTIVES: This study aims to synthesize real-world evidence and evaluate the effectiveness and safety of first-line therapies for advanced HCC in real-world scene, and provide complementary decision-making evidence to RCTs.
METHODS: A systematic search was performed across 7 databases (i.e., PubMed, Embase, Cochrane Library, CNKI, Wan Fang, VIP and CBM), with a time horizon from inception through December 2024. Only real-world studies were included, and treatments were selected in one of the five Guideline-recommended therapies: Atezolizumab-Bevacizumab, Sintilimab-Bevacizumab biosimilar, Lenvatinib, Donafenib and Sorafenib. Outcomes included hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR). Adverse effects (AEs) and serious adverse events (SAEs) were included for safety evaluation. The Newcastle-Ottawa scale (NOS) was used for quality assessment and R 4.4.3 to implement the Bayesian model network meta-analysis (NMA). Meta-analysis based on RCTs were also searched for comparison.
RESULTS: 25 studies met inclusion criteria which included 4 treatments: Atezolizumab-Bevacizumab, Sintilimab-Bevacizumab biosimilar, Lenvatinib and Sorafenib. NOS ratings indicated high quality in 23 studies. Compared with Sorafenib, Lenvatinib demonstrated significant advantages in PFS (HR=0.62, 95%CrI 0.49-0.78), ORR (OR=5.0, 95%CrI 3.3-7.5) and DCR (OR=2.2, 95%CrI 1.8-2.7), Atezolizumab-Bevacizumab showed improvement in ORR (OR=3.9, 95%CrI 2.4-6.6) and DCR (OR=2.2, 95%CrI 1.6-2.9). Safety analysis revealed no significant result in AEs/SAEs incidence across all therapies. In comparison with results in meta-analysis based on RCT, both studies proved effectiveness of Lenvatinib. However, Atezolizumab-Bevacizumab showed significant advantage observed in RCTs rather in real-world, and safety profiles diverged between real-world data and RCTs.
CONCLUSIONS: This systematic review and NMA synthesize real-world evidence and find limited advantages among Atezolizumab-Bevacizumab, Lenvatinib, Sintilimab-Bevacizumab biosimilar and Sorafenib in clinical effectiveness or safety. The comparison to RCT based Meta-analysis proves the effectiveness of Lenvatinib while highlighted heterogeneity in Atezolizumab-Bevacizumab effectiveness outcomes and overall discrepancies in safety profiles.