Adjuvant tyrosine kinase inhibitors plus anti‑PD‑1 therapy reduce recurrence in high-risk hepatocellular carcinoma after resection

Jiaxin Li¹Yukun Sun¹Ziniu Liu¹Jianwen Huang¹Jian Wu²Yun Huang¹Yali Gao^1*Baomin Chen^2*Qiang He^2*

• ¹The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
• ²Sun Yat-sen University First Affiliated Hospital Department of Pancreato Biliary Surgery, Guangzhou, China

Background/Aims: No standardized adjuvant treatment has been established for patients with hepatocellular carcinoma (HCC) following curative resection. This study aimed to evaluate the efficacy and safety of adjuvant tyrosine kinase inhibitors (TKIs) in combination with anti-programmed death-1 (PD-1) antibody in HCC patients with high-risk factors for recurrence. Methods: HCC patients who underwent hepatectomy at the First Affiliated Hospital, Sun Yat-sen University between January 2020 and December 2022 were retrospectively enrolled. Baseline differences were balanced between HCC patients with adjuvant therapy group (TKIs+PD-1, AT group) and hepatectomy alone group (HA group) by propensity-score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were compared between these two groups. Univariable and multivariable analyses were used to identify prognostic factors, and a subgroup analysis was also conducted to assess treatment efficacy across different patient subpopulations. Results: A total of 357 HCC patients with high risk of recurrence was enrolled. After PSM, 50 matched pairs of patients were analyzed. After PSM, the median follow-up was 30.2 months (IQR 18.47–37.48). The median RFS was 25.77 months (95% CI: 15.07- not evaluated (NE)) in the AT group versus 7.7 months (95% CI: 5.43-15.2) in the HA group. The AT group demonstrated significantly longer RFS compared with the HA group (P=0.0029), while no significant difference in OS was observed (P=0.62). Multivariable analyses identified adjuvant therapy with TKIs and anti-PD-1 antibodies as an independent protective factor for RFS, but not for OS. Subgroup analysis further confirmed the RFS benefit of adjuvant combination therapy in patients with high-risk factors, without a corresponding improvement in OS. Conclusions: Adjuvant TKIs combined with anti-PD-1 antibody significantly prolongs recurrence-free survival in HCC patients with high risk of postoperative recurrence. However, this combination does not confer a survival benefit in terms of overall survival. These findings support the potential clinical utility of adjuvant targeted immunotherapy in this high-risk population and highlight the need for further validation in prospective, randomized studies.