Comparative Efficacy of Initial Treatment Strategies in Patients With Tace-Unsuitable Hepatocellular Carcinoma

BACKGROUND AND AIMS: Transarterial chemoembolisation (TACE) is considered the standard-of-care for patients with intermediate-stage hepatocellular carcinoma (HCC), despite several patients exhibit features that may be associated with suboptimal outcome of treatment– also referred to as TACE-unsuitable. In this study our aim was to provide real-world evidence that patients who are considered TACE-unsuitable may receive greater benefit by systemic therapy than by TACE. METHODS: This study analysed 1,150 patients with TACE-unsuitable HCC, defined according to Asia-Pacific Primary Liver Cancer Expert criteria. Patients were initially treated with TACE (n=842), sorafenib (n=96), lenvatinib (n=62), or atezolizumab/bevacizumab (n=47). Overall survival (OS) was the primary endpoint. Inverse Probability of Treatment Weighting was applied to adjust for baseline differences. RESULTS: Compared to TACE, atezolizumab/bevacizumab reduced mortality risk [Hazard Ratio (HR): 0.47, 95% Confidence Interval (95%CI): 0.27–0.80; p=0.008), lenvatinib was neutral (HR 0.62, 95%CI: 0.35–1.08; p=0.091), and sorafenib was associated with increased mortality (HR 1.85, 95%CI: 1.28–2.65; p=0.001). OS at 24-month was 60.2% for TACE, 31.9% for sorafenib, 68.3% for lenvatinib, and 70.5% for atezolizumab/bevacizumab (p<0.0001). The disease control rate was 53.2% with TACE, 47.9% with sorafenib, 67.8% with lenvatinib (p=0.030 versus TACE; p=0.025 versus sorafenib), and 75.6% with atezolizumab/bevacizumab (p<0.001 versus TACE; p<0.001 versus sorafenib). CONCLUSIONS: In TACE-unsuitable patients, systemic treatment with atezolizumab/bevacizumab and, to a lesser extent, with lenvatinib, is associated with improved outcome compared to TACE. These findings support a paradigm shift in the initial management of intermediate-stage HCC favouring the early use of systemic therapy in appropriately selected patients.