To evaluate the efficacy of TACE-hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and PD-1 inhibitor in the treatment of stage Ⅲa liver cancer.

Clinical data of 96 patients with stage Ⅲa liver cancer admitted to Cancer Hospital of Guangzhou Medical University from January 2020 to May 2023 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 86 patients were male and 10 female, aged from 33 to 74 years, with a median age of 54 years. All patients were classified as CNLC stage Ⅲa. According to different treatment protocols, all patients were divided into the quadruple-treatment group (n=62) and triple-treatment group (n=34). In the quadruple-treatment group, patients were treated with TACE-HAIC combined with lenvatinib and PD-1 inhibitor, and those in the triple-treatment group were treated with TACE-HAIC combined with lenvatinib. Inter-group equilibrium was obtained by 1∶1 propensity score matching (PSM). Primary end points were overall survival (OS) and progression-free survival (PFS). The incidence of adverse reactions between two groups was compared by Chi-square test or Fisher’s exact test. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The influencing factors of survival were identified by Cox proportional hazard regression model.

After PSM, the median OS in the quadruple-treatment group was 32.0 months (95%CI: 10.985-53.015), and 14.0 months in the triple-treatment group (95%CI: 6.548-21.452), and the difference was statistically significant (χ²=9.071, P=0.003). The median PFS in the quadruple-treatment group was 19.0 months (95%CI: 9.655-28.345), and 6.0 months in the triple-treatment group (95%CI: 3.197-8.803), and the difference was statistically significant (χ²=7.811, P=0.005). Cox’s regression analysis showed that treatment method (HR=0.318, 95%CI: 0.144-0.701; P=0.004) and frequency of TACE-HAIC (HR=0.415, 95%CI: 0.197-0.873; P=0.020) were the independent influencing factors of OS. Treatment method was an independent influencing factor of PFS (HR=0.439, 95%CI: 0.238-0.810; P=0.008). No toxicity-related death occurred in this study. No significant difference was found in the incidence of any grade and grade 3/4 adverse reactions (all P>0.05).

The quadruple therapy of TACE-HAIC combined with lenvatinib and PD-1 inhibitor can significantly improve the survival benefit of patients with stage Ⅲa liver cancer without sacrificing the incidence of adverse reactions.