Comparison of tumor response and outcomes of patients with hepatocellular carcinoma after multimodal treatment including immune checkpoint inhibitors – a systematic review and meta-analysis

Abstract

Background

The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC.

Methods

PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990–2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported.

Results

Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83–91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%–89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09–9.63), ICI + TKI (OR 3.08, 95% CI 1.63–5.82), and TKI + TACE (OR 2.90, 95% CI 1.61–5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37–1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70–1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29–0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05).

Conclusion

The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC.