Efficacy and safety of postoperative adjuvant HAIC combining lenvatinib with or without PD-1 inhibitors in solitary large HCC: a multicenter retrospective study

Yuxin Liang^1,2Min Wang¹Deyuan Zhong^1,2Hongtao Yan¹Yuhao Su¹Xing Chen³Xiaolun Huang^1*Zhengwei Leng^1,4*

• ¹Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China
• ²Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
• ³State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, SAR China
• ⁴Department of Hepatobiliary Surgery (Ⅱ), Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, Shanxi Province, China

Purpose: To evaluate the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC) combined with lenvatinib and PD-1 inhibitors versus PA-HAIC with lenvatinib alone in patients with solitary large hepatocellular carcinoma (HCC, >5 cm). Methods: A total of 183 patients who underwent curative resection and subsequent PA-HAIC plus lenvatinib (HAIC-L, n = 108) or PA-HAIC combined with lenvatinib and PD-1 inhibitors (HAIC-L-P, n = 75) were enrolled from three centers between April 2021 and April 2023. Propensity score matching (PSM) was applied to balance baseline characteristics. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox proportional hazards models, while treatment-related adverse events (TRAEs) were compared between groups. Results: The HAIC-L-P group demonstrated significantly improved DFS compared to the HAIC-L group both before (HR: 0.570; P = 0.007) and after PSM (HR: 0.518; P = 0.018). In contrast, no statistically significant difference was observed in OS between the two groups. Multivariate analysis identified elevated AFP (≥400 ng/mL), microvascular invasion, and treatment strategy (HAIC-L vs. and HAIC-L-P) as independent predictors of DFS. Additionally, the overall safety profiles were comparable, with similar incidences of TRAEs and no significant increase in hepatic toxicity with PD-1 inhibitor addition. Conclusion: PA-HAIC combined with lenvatinib and PD-1 inhibitors significantly enhances DFS in patients with solitary large HCC, offering a promising adjuvant approach with acceptable safety. Further prospective, biomarker-driven trials are warranted to validate these findings and optimize patient selection.