1003P - Efficacy and safety of triple combination therapy with transarterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and immune checkpoint inhibitor (ICI) versus dual combination therapy in unresectable hepatocellular carcinoma (uHCC): A systematic review and meta-analysis

Background

Multimodal approach, a combination of various treatment modalities, has emerged as a potential approach for treating uHCC. It is utilized to help relieve tumor burden, slow progression, and provide survival benefits to patients. However, controversies remain in using a multimodal approach in the management of uHCC, and is still debatable. This study aims to evaluate the efficacy and safety of triple combination therapy composed of Transarterial chemoembolization (TACE), TKI, and ICI compared to dual combination therapy (TACE+TKI, TKI+ICI).

Methods

Eligible studies published before March 30, 2023 were retrieved. Outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and occurrence of adverse events (AEs). Literature search was done using through PubMed, Embase, and Cochrane Library. Risk of bias assessment was done using ROBINS-I tool.

Results

Thirteen retrospective studies were included representing 1005 patients with uHCC. There was low to moderate bias among the studies. Triple combination therapy was associated with a significant improvement in survival compared to dual combination therapy: median OS, pooled HR 0.46 (95% CI: 0.39-0.54, p<0.00001) and median PFS, pooled HR 0.41 (95% CI: 0.28-0.61, p<0.00001). Triple combination therapy was also associated with a significant increase in tumor response compared to dual combination therapy: ORR, pooled RR 1.76 (95% CI: 1.51-2.06, p<0.00001), and DCR, pooled RR 1.36 (95% CI 1.24-1.49, p-<0.00001). However, triple combination therapy had a higher risk of adverse events compared to dual combination therapy, pooled RR 1.49 (95% CI: 1.19, 1.86, p=0.0004). There was no significant heterogeneity found among the studies included.

Conclusions

Triple combination therapy was associated with significantly better outcomes but higher risk of adverse events than dual combination therapy in patients with uHCC so careful consideration of the risks and benefits must be done before initiating treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.