Comparative efficacy and safety of molecular targeted agents combined with transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: a network meta-analysis

Abstract

ObjectiveAt present, several molecular targeted agents(MTAs) combined with transarterial chemoembolization (TACE) have been employed to treat unresectable hepatocellular carcinoma (HCC). In this meta-analysis, we compared the efficacy and safety of different MTAs combined with TACE to enable effective decision-making for the clinical treatment of unresectable HCC.MethodsPubmed, Web of Science, EMBASE, and Cochrane Library were retrieved to evaluate the efficacy and safety of different MTAs combined with TACE in cohort studies and randomized controlled trials. The hazard ratios and 95% confidence intervals (CIs) were calculated to investigate the impact of various therapies on overall survival (OS) and progression-free survival. However, the objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and ≥grade-3 adverse events (≥G3-AEs) were calculated using odd ratios and 95% CIs. The node-splitting approach was used to test the heterogeneity. The funnel plot was utilized to analyze the publication bias. Additionally, according to the ranking plots, we ranked various treatments.ResultsA total of 45 studies involving 10,774 patients with 8 treatment strategies were included in our network meta-analysis. Our network meta-analysis showed that apatinib+TACE provided the highest OS (62.2%), ORR (44.7%), and DCR (45.6%), while and lenvatinib+TACE offered the best PFS (78.9%). Besides, there was no statistically significant difference in AEs and ≥G3-AEs among treatment options.ConclusionApatinib+TACE demonstrated the best OS, ORR, and DCR with no additional AEs and ≥G3-AEs. Therefore, for the treatment scheme of MTAs combined with TACE, apatinib+TACE may be the best option for patients with unresectable HCC.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023388609.

Lenvatinib in combination with transarterial chemoembolization vs. sorafenib in combination with transarterial chemoembolization for unresectable hepatocellular carcinoma: A network meta‑analysis

“…Furthermore, there were no significant differences in the survival advantage between sorafenib with TACE and lenvatinib monotherapy in the present NMA. Similar results have been reported by other studies ( 16 , 30 , 33 ). However, considering the increased survival outcomes of lenvatinib monotherapy compared with sorafenib monotherapy and the lack of a direct comparison between lenvatinib and sorafenib with TACE in the currently available studies, more head-to-head research is needed to further explore the superiority of survival outcomes ( 12 , 34 ).…”

“…A recent NMA included 10 RCTs and 35 cohort studies and compared the efficacy and safety of TKIs in combination with TACE in the treatment of uHCC ( 16 ). The lenvatinib with TACE combination therapy had a significantly longer PFS (HR, 0.53; 95% CI, 0.32–0.88) but not OS (HR, 0.88; 95% CI, 0.65–1.13), when compared with sorafenib with TACE group.…”

“…High heterogeneity (consistency model, I2=69%; inconsistency model, I2=66%) was observed in OS under the fixed-effects model. The commonality between the two aforementioned NMAs was that non-RCTs accounted for the majority of the included studies, which may be the underlying cause of the inaccurate results ( 16 , 29 ).…”

“…However, in our previous meta-analysis, the use of lenvatinib with TACE was significantly superior compared with sorafenib with TACE, in terms of OS, PFS and tumor response in patients with uHCC ( 15 ). In contradiction to the aforementioned results, a further network meta-analysis (NMA) reported no statistically significant difference between the use of lenvatinib with TACE compared with sorafenib with TACE in terms of OS ( 16 ). A large proportion of studies included in the aforementioned meta-analyses were retrospective cohort studies, which could have introduced the potential risk of selection bias and confounding bias.…”

Efficacy of Lenvatinib Combined with Transcatheter Intra-Arterial Therapies for Patients with Advanced-Stage of Hepatocellular Carcinoma: A Propensity Score Matching

“…LEN specifically targets vascular endothelial growth factor receptors (VEGF) 1–3 and fibroblast growth factor receptors (FGFR) 1–4, offering the potential for a higher response rate compared to other MTAs [ 6 ]. However, as the therapeutic effect of LEN monotherapy in patients with u-HCC is limited, there is growing interest in exploring the strategy of combining LEN with other therapies [ 7 , 8 ]. We previously reported that the combination of LEN with transcatheter intra-arterial therapies (TIT), such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC), improved the prognosis of patients with intermediate-stage HCC [ 9 ].…”