Abstract
In this editorial, we comment on the article (World J Gastrointest Oncol 2024; 16: 1236-1247), which is a retrospective study of transarterial chemoembolization (TACE) combined with multi-targeted tyrosine kinase inhibitor (TKI) and programmed cell death protein-1 (PD-1) inhibitor for the treatment of unresectable hepatocellular carcinoma (HCC). Herein, we focus specifically on the mechanisms of this triple therapy, administration sequence and selection of each medication, and implications for future clinical trials. Based on the interaction mechanisms between medications, the triple therapy of TACE + TKI + PD-1 is proposed to complement the deficiency of each monotherapy, and achieve synergistic antitumor effects. Although this triple therapy has been evaluated by several retrospective trials, it is still controversial whether the triple therapy achieves better clinical benefits, due to the flawed study design and heterogeneity in medications. In addition, the administration sequence, which may greatly affect the clinical benefit, needs to be fully considered at clinical decision-making for obtaining better prognosis. We hope that this editorial could contribute to the design and optimization of future trials.