Comprehensive evaluation of immunotherapy combination approaches versus tyrosine-kinase inhibitor monotherapy for the treatment of hepatocellular carcinoma: A meta-analysis.

Abstract

574 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and first-line treatment options for advanced stages remain limited. Our study aims to evaluate the effectiveness and safety of different immunotherapy combination approaches in the treatment of HCC. Methods: We retrieved data from clinical trials published between 2018 and 2025. Individual patient data was extracted from already published Kaplan-Meier (KM) curves to permit comparisons across studies. A meta-analysis was performed to assess patient demographics, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events (AEs). Results: Our analysis included a total of 3,312 patients, of whom 878 received an immune checkpoint inhibitor (ICPI) in combination with bevacizumab, 705 received ICPI combined with a tyrosine-kinase inhibitor (TKI), and 1,729 were treated with TKI monotherapy. The median OS was 19.09 months (95% CI: 17.09-21.27) for the ICPI+ bevacizumab group, 19.22 months (95% CI: 16.82-21.88) for the ICPI+ TKI group, and 15.29 months (95% CI: 13.96-16.27) for the TKI monotherapy group. Corresponding median PFS values were 5.76 months (95% CI: 5.55-6.74), 6.17 months (95% CI: 5.59-7.07), and 5.43 months (95% CI: 4.77-5.52), respectively. Regarding safety profile, the overall incidence of grade III/IV AEs was most common in the ICPI+ TKI group (72.35%), followed by TKI monotherapy (42.73%) and ICPI+ bevacizumab (38.65%) (p=0.1035). Hypertension (26.14% versus ~8%, p=0.0041), diarrhea (2.84%, p=0.0024), and platelet abnormalities (10.09%, p<0.0001) were significantly higher in the ICPI+ TKI group. Anemia was more frequent with ICPI+ bevacizumab (5.56%, p=0.0275). Other AEs showed no significant difference. Conclusions: Our analysis demonstrated improved OS in ICPI combinations with bevacizumab or TKIs in advanced HCC. However, the ICPI+ TKI combination regimen was associated with a higher incidence of certain AEs, which highlights the need to balance the efficacy and tolerability in the management of advanced HCC.