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

## TL;DR

Adding a PD-1 antibody to cryoablation and Renvastinib improves survival and treatment response in patients with unresectable liver cancer without increasing side effects.

## Contribution

Triple therapy with PD-1 mAb, cryoablation, and Renvastinib shows improved efficacy and safety for unresectable hepatocellular carcinoma.

## Key findings

- Triple therapy significantly improved objective response and disease control rates compared to double therapy.
- Triple therapy led to better progression-free and overall survival in uHCC patients.
- No significant difference in adverse events between the two treatment groups.

## Abstract

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).

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 t 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.

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%, P=0.08; DCR: P=0.003; 86.1% vs. 64.1%). Compared to the double group, the OS and PFS rates in the triple group were considerably higher (P=0.045 and P=0.026, respectively). Analysis of univariate and multivariable Cox risk proportional models showed that AFP level (HR=2.37, P=0.001) and treatment regimen (HR=0.60, P=0.38) were independent risk factors for OS. Independent risk variables for PFS included diabetes mellitus (HR=1.94, P=0.05), prior local treatment (HR=0.63, P=0.014), treatment protocol (HR=0.65, P=0.025), and distant metastasis (HR=0.58, P=0.09). The incidence of negative reactions did not differ significantly between the two groups (P>0.05).

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.