Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-associated mortality globally (Sung et al., 2021). Most patients diagnosed with HCC present at an advanced stage, making curative treatment options, such as surgical resection or liver transplantation, non-feasible (Forner, Reig, & Bruix, 2018). The prognosis of patients with unresectable HCC (uHCC) remains poor, underscoring the urgent need for effective systemic treatments (Llovet, Montal, Sia, & Finn, 2018). In the past decade, substantial advances have been made in therapeutic approaches to uHCC, ranging from localized to systematic treatments. These include chemotherapy, transarterial chemoembolization (TACE), external-beam radiation therapy, targeted therapy, and immunotherapy (Gordan et al., 2020).

Lenvatinib, an oral multikinase inhibitor targeting vascular endothelial growth factor receptors, has been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with uHCC (Ikeda et al., 2017; Kudo et al., 2018). TACE, a locoregional therapy that combines embolization and chemotherapy, has also demonstrated efficacy for the treatment of uHCC by selectively occluding tumor-feeding arteries and delivering high concentrations of chemotherapeutic agents (Chung et al., 2011). The most recent evidence from the TACTICS trial confirmed that a synergistic approach using TACE and sorafenib could notably extend TACE-specific PFS and yield a clinically significant increase in OS in patients with uHCC (Kudo et al., 2020). Moreover, combination therapy with lenvatinib and TACE has yielded a higher response rate and more favorable survival outcomes than the solitary use of TACE in patients bearing substantial tumor loads (Fu et al., 2021; Kudo et al., 2020).

Recently, the clinical use of immune checkpoint inhibitors (ICIs), including those targeting programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1), has demonstrated promising results in patients with advanced HCC. Although anti-PD-1 monotherapy did not achieve its primary survival goals in phase III trials (Finn et al., 2020; Yau et al., 2022), combined therapies involving PD-1/PD-L1 inhibitors and anti-angiogenic agents have yielded intriguing outcomes (Finn et al., 2020; Ren et al., 2021). The therapeutic combination of TACE and lenvatinib with a PD-1 inhibitor may enhance antitumor efficacy by increasing tumor immunogenicity and promoting immune-mediated tumor destruction. However, evidence supporting the concomitant use of TACE, lenvatinib, and PD-1 inhibitors in advanced HCC remains limited. As such, this meta-analysis aimed to synthesize the available evidence to evaluate the effectiveness and safety of TACE in conjunction with lenvatinib and PD-1 inhibitors for the treatment of advanced HCC, and to test whether the data accumulated provided sufficient power to assess intervention effects.