Abstract
The treatment options for patients with unresectable HCC who are refractory/ intolerant/ contraindicated to TACE (‘ineligible for TACE’) include systemic therapy and selective internal radiation therapy (SIRT). This study assesses the comparative efficacy of treatments in this population through an indirect treatment comparison. The feasibility of the network meta-analysis (NMA) included assessment of the variability of the population in randomised controlled trials identified by a systematic literature review. Comparators were selected based on the National Institute for Health and Care Excellence and clinical guidelines and clinical practice.Random and fixed-effects (RE, FE) Bayesian NMAs were conducted to assess hazard ratios (HR) of overall survival (OS). Two studies, SARAH and REFLECT, were included in the network, with sorafenib as the common comparator for SIRT with Y-90 resin microspheres and lenvatinib, respectively. Eligibility criteria differed between trials: REFLECT excluded patients with main portal vein thrombosis (PVT) and included patients with extrahepatic spread (EHS); SARAH included patients with main PVT and excluded patients with EHS. Clinical experts confirmed these differences should be adjusted for. Results from both trials for patients without EHS or any PVT were analysed. Based on FE analyses, the OS HR for SIRT vs. sorafenib was 1.05 (Credible Interval: 0.75,1.46), for lenvatinib vs. sorafenib was 1.05 (0.79,1.39), and for SIRT vs. lenvatinib was 1.00 (0.29, 3.53). For the unselected populations, the FE OS HR for SIRT vs. sorafenib was 1.15 (0.94,1.40) and lenvatinib vs. sorafenib was 0.92 (0.79,1.06). RE results with an informative prior were similar. When accounting for the most important differences between trials, the effectiveness of treatments for the unresectable HCC population ineligible for TACE is very similar. There were no statistically significant differences (p<0.05) in efficacy between treatments in either analysis.
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