Transarterial chemoembolization combined with PD-1 inhibitors for unresectable hepatocellular carcinoma: efficacy and hepatic safety at 4-week versus 6-week treatment intervals.

OBJECTIVE: To compare the effect of 4-week and 6-week transarterial chemoembolization (TACE) intervals on tumor response and liver function in patients with unresectable hepatocellular carcinoma (HCC) receiving TACE plus programmed death-1 (PD-1) inhibitor combination therapy. METHODS: A total of 186 patients with unresectable HCC who underwent TACE combined with PD-1 inhibitor therapy were enrolled in this retrospective study. All patients were categorized into two groups according to TACE treatment intervals: the 4-week interval group (n=92) and the 6-week interval group (n=94). Baseline demographic and clinical data were collected for all participants. Hepatic and renal function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), creatinine (Cr), and blood urea nitrogen (BUN), as well as serum tumor markers consisting of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125), were detected at baseline and one month after treatment initiation. Tumor response was evaluated at three months post-treatment based on the RECIST 1.1, and the objective response rate (ORR) and disease control rate (DCR) were calculated accordingly. Treatment-related adverse events (AEs) were documented and graded in accordance with the CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of treatment to death or disease progression, with continuous follow-up until the study endpoint. RESULTS: The 186 enrolled patients were well-balanced in baseline clinicopathologic characteristics between the two groups. Compared to the 6-week group, the 4-week group achieved significantly higher ORR (35.87% vs. 22.34%, P=0.042) and DCR (81.52% vs. 67.02%, P=0.024), a more substantial reduction in AFP level, and markedly prolonged median OS and PFS (all P<0.001). Nevertheless, the 4-week group presented significantly elevated ALT levels (P=0.001) and decreased ALB levels (P=0.012) at one month post-treatment. Multivariate Cox regression analysis identified the 4-week interval as an independent favorable prognostic factor for OS (HR=0.692, 95% CI 0.498-0.961, P=0.029). The overall incidence of AEs was comparable between the two groups. CONCLUSION: For patients with unresectable HCC treated with TACE combined with PD-1 inhibitors, a 4-week TACE interval yielded superior tumor response and survival benefits with acceptable hepatic safety compared to a 6-week interval, which supports the 4-week interval as an optimal clinical treatment schedule.