Efficacy and Safety Analysis of Triple Therapy (Pabolizumab+Cryoablation+Renvastinib) for Patients with Unresectable Hepatocellular Carcinoma (uHCC).

[BACKGROUND] To determine whether employing a monoclonal antibody against programmed death receptor-1 (PD-1) improves the safety and effectiveness of cryoablation used with Renvastinib to treat unresectable hepatocellular carcinoma (uHCC).

[METHODS] Our study retrospectively enrolled 232 uHCC patients who were treated at our medical center between January 2019 and December 2023. Propensity score matching (PSM) was employed in this study for 1:1 matching, and 86 patients were matched in each group. Following matching, the two groups' negative events, and assessments were made on the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). When comparing two groups, a group test was employed to determine whether the quantitative data were normally distributed. The two groups' survival rates were calculated using the Kaplan-Meier method, survival curves were made, and the log-rank test was performed to find differences between the two groups.

[RESULTS] The median follow-up period was 28 months. Forty deaths (46.0%) happened in the double group, whereas 33 deaths (38.0%) occurred in the triple group. The ORR and DCR of the triple treatment group were significantly higher than those of the double therapy group (ORR: 35.6% vs. 14.5%, =0.08; DCR: =0.003; 86.1% vs. 64.1%). Compared to the double group, the OS and PFS rates in the triple group were considerably higher (=0.045 and =0.026, respectively). Analysis of univariate and multivariable Cox risk proportional models showed that AFP level (HR=2.37, =0.001) and treatment regimen (HR=0.60, =0.38) were independent risk factors for OS. Independent risk variables for PFS included diabetes mellitus (HR=1.94, =0.05), prior local treatment (HR=0.63, =0.014), treatment protocol (HR=0.65, =0.025), and distant metastasis (HR=0.58, =0.09). The incidence of negative reactions did not differ significantly between the two groups (>0.05).

[CONCLUSION] Compared with cryoablation combined with renvatinib, cryoablation combined with renvatinib and PD-1 mAb significantly improved the efficacy and survival of patients with uHCC without increasing adverse events, giving unresectable liver cancer a clinical foundation for treatment optimization.