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 IOIO 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.

Automated summary

We aimed to determine the optimal treatment option for advanced hepatocellular carcinoma (HCC), considering systemic therapy with or without locoregional therapy. 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 adverse events were the outcomes of interest. The surface under the cumulative ranking curve (SUCRA) probability values were used to rank the interventions. In total, 23 randomized-controlled trials with 14,303 patients were included. Lenvatinib plus transcatheter arterial chemoembolization (TACE) ranked best in terms of 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 compared to IOIO 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.