Systemic therapy with or without locoregional therapy for advanced hepatocellular carcinoma: A systematic review and network meta-analysis.

We aim to identify the optimal treatment option of systemic therapy with or without locoregional therapy for advanced hepatocellular carcinoma (HCC). Outcomes of interest include overall survival (OS), progression-free survival (PFS), objective response rate (ORR), grade 3–4 treatment-related adverse events (TRAEs), and incidence of treatment discontinuation due to AEs. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the interventions. 23 randomized-controlled trials including 14,303 patients with advanced HCC were included. Lenvatinib plus transcatheter arterial chemoembolization (TACE) ranked best regarding OS benefit (SUCRA: 0.99). Immuno-oncology (IO)-multikinase inhibitor (MKI)/vascular endothelial growth factor (VEGF) inhibitor combinations had a higher probability of providing better OS than IO-IO combinations. IO monotherapies demonstrated superior safety profile while combination therapies caused more toxicity in general. We conclude that combination therapies achieve remarkable efficacy in patients with advanced HCC and clinical decision making requires a careful balance of efficacy versus risk. • IO-MKI/VEGF combinations exhibit better survival outcomes than IO-IO combinations. • The efficacy and safety profiles of ICI-MKI and ICI-VEGF could be comparable. • Len-Pem is superiority to sorafenib regarding OS, PFS, and ORR. • Efficacy of LEN-TACE and Sora-HAIC is yet to be confirmed in western populations. • Combination therapies improve prognosis but with more toxicity than monotherapies. [ABSTRACT FROM AUTHOR]