To evaluate clinical efficacy and safety of lenvatinib and PD-1 inhibitor pretreatment combined with TACE sequential therapy for CNLC stage Ⅲ hepatocellular carcinoma (HCC).

Clinical data of 57 patients diagnosed with CNLC stage Ⅲ HCC in Henan Provincial People's Hospital from January 2021 to December 2022 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 43 patients were male and 14 female, aged from 34 to 74 years, with a median age of 57 years. According to different treatment regimens, they were divided into two groups. In the LenPT group (n=19), lenvatinib and PD-1 inhibitor pretreatment were given, followed by TACE sequential therapy. In the TaLP group (n=38), TACE therapy was delivered, followed by lenvatinib and PD-1 inhibitor treatment. Clinical efficacy, influencing factors and safety between two treatment regimens were observed. Liver function and albumin-bilirubin (ALBI) score in two groups were compared by t-test or rank sum test. Disease control rate (DCR) between two groups was compared by Chi-square test. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The influencing factors of survival were analyzed by Cox regression models.

After 6-month treatment, the DCR in the LenPT group was 89%(17/19), significantly higher than 50%(19/38) in the TaLP group (χ²=8.482, P=0.004). The median progression-free survival (PFS) in the LenPT group was 9.0 months, significantly longer than 6.0 months in the TaLP group (χ²=5.106, P=0.024). Multivariate Cox regression analysis showed that treatment regimen was an independent influencing factor of PFS (HR=1.956, 95%CI: 1.025-3.732; P=0.042). At 5-7 d after the first TACE, the ALT level in the LenPT group was 58(40-81) U/L, significantly lower than 80(60-96) U/L in the TaLP group (Z=-2.015, P<0.05). In the LenPT group, the ALBI score at 1 year after treatment was (-1.96±0.34), significantly lower than (-1.30±0.22) in the TaLP group (t=-6.666, P<0.001). In the LenPT group, Child-Pugh score was 6(5-7), significantly lower than 8(7-9) in the TaLP group (Z=-3.918, P<0.05). All adverse reactions during the treatment were relieved after corresponding treatment in two groups.

Compared with TACE followed by lenvatinib and PD-1 inhibitor treatment, lenvatinib and PD-1 inhibitor pretreatment combined with TACE sequential therapy can improve DCR, prolong PFS, alleviate liver function damage of patients with CNLC stage Ⅲ HCC. In addition, adverse events are generally controllable, indicating that this procedure is safe and efficacious in clinical practice.