Transarterial chemoembolization plus donafenib and immune checkpoint inhibitors for intermediate hepatocellular carcinoma (CHANCE2410): A propensity score matching analysis.

4126 Background: Hepatocellular carcinoma (HCC) has high incidence and mortality, with over 80% of patients diagnosed at intermediate or advanced stages, limiting surgical options and worsening prognosis. Transarterial chemoembolization (TACE) is the standard treatment for intermediate HCC, inducing tumor ischemia and hypoxia, which alters the immune microenvironment and promotes immune activation. Combining TACE with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has shown promise in enhancing treatment efficacy. Trials like EMERALD-1 and LEAP-012, along with real-world studies, suggest that TACE plus ICIs and TKIs improves progression-free survival (PFS) in intermediate HCC patients compared to TACE monotherapy. Donafenib, an oral TKI, has shown superior overall survival compared to sorafenib, being recommended as first-line treatment for advanced HCC in China. However, large real-world studies on the combination of TACE plus donafenib and ICIs in intermediate HCC are scarce. This study aims to compare the efficacy and safety between the combination therapy and the TACE monotherapy for intermediate HCC in a real-world setting. Methods: This nationwide, multicenter, retrospective cohort study included patients with intermediate HCC receiving either combination therapy or TACE monotherapy between January 2021 and May 2024 in China. The primary outcome was PFS. The secondary outcomes included overall survival (OS) rate, objective response rate (ORR) and safety. Tumor response was evaluated according to the mRECIST criteria. 1:1 propensity score matching (PSM) analysis was employed to minimize bias. Cox proportional-hazards regression model was used to analyze factors affecting PFS and OS. Results: A total of 364 patients were enrolled, with 192 receiving combination therapy and 172 receiving TACE monotherapy. After PSM, 127 patients from each group were included for analysis. The median PFS were significantly longer in the combination therapy group than it in the TACE monotherapy group (19.6 months [95% CI, 14.9-24.4] vs. 15.3 months [95% CI, 12.8-17.8], HR 0.647 [95% CI, 0.464–0.903], p = 0.010). The OS rate was higher in the combination therapy group (94.8% vs. 83.5%, 1-year OS rate; 76.4% vs. 64.8%, 2-year OS rate; HR 0.542 [95% CI, 0.327–0.989], p = 0.016). The ORR was also higher in the combination therapy group (78.9% vs. 62.5%, p = 0.002). Grade 3 or 4 adverse events from any cause were observed at a rate of 12.5% and 5.5% in the combination and monotherapy groups, respectively. Multivariate analysis identified combination therapy as an independent prognostic factor for both longer PFS and OS. Conclusions: Compared to TACE monotherapy, TACE plus donafenib and ICIs offers superior OS and PFS, which may be a viable first-line treatment option for intermediate HCC.