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

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.