Efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC): A systematic review and meta-analysis

Background The optimal management of unresectable hepatocellular carcinoma (uHCC) remains an unresolved challenge. There is ongoing debate regarding the efficacy and safety of drug-eluting bead TACE (DEB-TACE) with tyrosine kinase inhibitors (TKIs). Methods We searched PubMed, Embase, Web of Science and the Cochrane Library for eligible studies. The main endpoints under investigation were survival outcomes, including overall survival (OS), progression-free survival (PFS), and time to progression (TTP). Secondary outcomes encompassed tumor response rates and adverse events (AEs). Two researchers conducted the data extraction independently and assessed the quality of the studies. After pooling and analyzing the data, we assessed the heterogeneity and performed both subgroup analysis and sensitivity analysis. Additionally, we evaluated the potential for publication bias. Results Eight studies with 1513 patients were finally retrieved. Compared to monotherapy, although bigeminal therapy exhibited improved survival benefits (OS: HR: 0.56, 95% CI 0.41-0.76, p<0.001; TTP: HR: 0.72, 95% CI 0.59-0.87, p = 0.001) and tumor response (ORR: RR: 1.59; 95% CI 1.19-2.13, p = 0.002; DCR: RR: 1.14; 95% CI 1.03-1.26, p = 0.010), the reliability of results was affected by significant heterogeneity. In the subgroup analysis, compared to DEB-TACE alone, the bigeminal therapy failed to show any statistical differences. Compared to TKIs, it demonstrated significant advantages in both survival (OS: HR: 0.49, 95% CI 0.40–0.61, p<0.001; TTP: HR: 0.60, 95% CI 0.48-0.75, p<0.001) and tumor response (ORR: RR: 2.40, 95% CI 1.86-3.09, p<0.001; DCR: RR: 1.36, 95% CI 1.20-1.54, p<0.001) while low heterogeneity was observed. Concerning safety, DEB-TACE provides no more severe AEs while TKIs-related AEs require close monitoring. Conclusion Our findings suggest that DEB-TACE combined with TKIs may be a safe and effective treatment for uHCC, which is more suitable for patients in the advanced stage.