Transarterial chemoembolization combined with tyrosine kinase inhibitors and programmed death-1 inhibitors in recurrent intermediate and advanced hepatocellular carcinoma: a single-centre retrospective cohort study.

BACKGROUND: We aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) plus tyrosine-kinase inhibitors (TKIs) with or without programmed death-1 (PD-1) inhibitors in recurrent intermediate-advanced hepatocellular carcinoma (HCC).

MATERIALS AND METHODS: In this retrospective, single-center cohort study (January 2016-January 2024), 39 consecutive patients with recurrent HCC (BCLC B/C) received TACE combined with (1) regorafenib (n = 14), (2) lenvatinib + PD-1 inhibitor (n = 12), or (3) regorafenib + PD-1 inhibitor (n = 13). Overall survival (OS) and progression-free survival (PFS) were primary outcomes. Objective response rate (ORR) and disease control rate (DCR) were secondary. Multivariable Cox regression and propensity score matching analyses were performed. A post-hoc power analysis was conducted to quantify statistical power.

RESULTS: Median follow-up was 36.5 months. Median OS and PFS for the entire cohort were 42.9 months (95% CI 27.1-58.7) and 16.5 months (95% CI 13.6-19.5), respectively. No significant differences in OS (P = 0.164) or PFS (P = 0.830) were observed among the three groups. ORR was 12.8% and DCR 51.3%. BCLC stage B (vs. C) was an independent favorable prognostic factor for OS (HR 0.03, P = 0.01) and PFS (HR 0.04, P = 0.038). Grade ≥ 3 adverse events occurred in 2 (5.1%) patients. The median number of TACE sessions was 4 (IQR 3-6) for Group A, 5 (IQR 3-7) for Group B, and 4 (IQR 3-5) for Group C (P = 0.72).

CONCLUSION: TACE plus TKIs with or without PD-1 inhibitors showed acceptable efficacy and safety in recurrent intermediate-advanced HCC. The addition of PD-1 inhibitors did not demonstrate additional survival benefit in this small cohort. However, the present sample size was underpowered to detect a clinically meaningful but modest survival difference. Prospective randomized trials are warranted.