To evaluate the clinical efficacy of the combination of lenvatinib, PD-1 inhibitor and transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) in the treatment of unresectable hepatocellular carcinoma (HCC).

Clinical data of69 HCC patients admitted to the Affiliated Cancer Hospital of Guangzhou Medical University from September 1, 2019 to February 1, 2021 were retrospectively analyzed. Among them, 64 patients were male and 5 female,aged (51±12) years on average. 37 patients were treated with lenvatinib, PD-1 inhibitor combined with TACE-HAIC (TAHPLa group), and 32 patients received sorafenib combined with TACE (SoraTACE group). The informed consents of all patients were obtained and the local ethical committee approval was received. The surgical conversion rate, tumor response, treatment-associated adverse reactions, and survival were observed between two groups. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The influencing factors of survival were identified by Cox's regression model.

In the TAHPLa group,surgical conversion rate was 30%(11/37), significantly higher than 3%(1/32) in the SoraTACE group (χ²=8.454, P<0.05). According to the modified response evaluation criteria in solid tumors (mRECIST), the objective remission rate in the TAHPLa group was 70%(26/37), significantly higher than 31%(10/32) in the SoraTACE group (χ²=10.470, P<0.05). Regarding the overall adverse events, the incidence of fatigue, nausea, sensory neuropathy and thrombocytopenia in the TAHPLa group was 46%(17/37), 54%(20/37), 27%(10/37) and 41%(15/37), significantly higher than 19%(6/32), 16%(5/32), 0 and 9%(3/32) in the SoraTACE group (χ²=5.711, 10.968, 8.051, 8.644; P<0.05); The hand-foot syndrome in the TAHPLa group was 8%(3/37), significantly lower than 28%(9/32) in the SoraTACE group (χ²=4.786, P<0.05). In terms of grade 3-4 adverse reactions, the incidence of thrombocytopenia in the TAHPLa group was 24%(9/37), significantly higher than 3%(1/32) in the SoraTACE group (χ²=4.630, P<0.05). No treatment-associated death occurred in both groups. In theTAHPLa group, the median progression-free survival (PFS) and overall survival (OS) were 10.3 and 27.8 months, compared with 5.1 and 10.7 months in the SoraTACE group, where significant differences were observed (χ²=10.871, 27.539; P<0.05). Cox's multivariate analysis showed that TAHPLa treatment was an independent influencing factor for the PFS and OS of patients (HR=0.053, 0.179; P<0.05).

Compared with sorafenib combined with TACE, combined treatment of lenvatinib, PD-1 inhibitor and TACE-HAIC is a safer therapy for unresectable HCC, which can enhance the surgical conversion rate and prolong the survival.