Introduction: 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 months 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, 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.
Keywords: Atezolizumab/bevacizumab; Locoregional treatment; Outcome; Systemic therapy; Tyrosine kinase inhibitors.
Hepatocellular carcinoma (HCC) is a type of liver cancer and patients with intermediate-stage HCC have tumours that are unlikely to respond well to a common local treatment called transarterial chemoembolisation (TACE), which delivers chemotherapy directly into the liver. Researchers wanted to find out whether those patients might live longer if they received newer drugs instead of TACE. This study looked at 1,150 patients in Italy who were considered “TACE-unsuitable” because of tumour size, liver function, or other characteristics. At the time of their first treatment, they received either TACE, the oral drugs sorafenib or lenvatinib, or an immunotherapy combination of atezolizumab and bevacizumab. The researchers adjusted the analysis to make sure the groups were comparable. The results showed that the immunotherapy combination reduced the risk of death by about half compared with TACE. Lenvatinib gave similar survival to TACE, while sorafenib did worse. After 2 years, about 70% of patients treated with immunotherapy were alive, compared with 68% of those taking lenvatinib, 60% of those receiving TACE, and 32% of those on sorafenib. The immunotherapy and lenvatinib groups also had better disease control, meaning their tumours stopped growing or shrank more often. These findings suggest that patients with intermediate-stage liver cancer who are unlikely to benefit from TACE might do better if they start with a systemic therapy, particularly the atezolizumab and bevacizumab combination or lenvatinib. Early use of these drugs could improve survival and control of the disease for this group of patients.
© 2026 The Author(s). Published by S. Karger AG, Basel.