The Safety and Efficacy of Hepatic Arterial Infusion Chemotherapy Combined with PD-(L)1 Inhibitors and Molecular Targeted Therapies for the Treatment of Intermediate and Advanced Hepatocellular Carcinoma Unsuitable for Transarterial Chemoembolization

Hao-Huan Tang,1,&ast; Ming-Qing Zhang,2,&ast; Zi-Chen Zhang,3,&ast; Chen Fan,1 Yong Jin,2 Wei-Dong Wang1 1Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Jin, Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67784269, Email jinyong@suda.edu.cn Wei-Dong Wang, Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299, Qingyang Road, Wuxi, 214023, People’s Republic of China, Tel/Fax +86 510 85350121, Email Wdoc@sina.comObjective: To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE).Methods: We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs).Results: A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0– 27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373– 6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492– 20.078, P < 0.001) were associated with the median OS.Conclusion: Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.Keywords: advanced hepatocellular carcinoma, hepatic arterial infusion chemotherapy, molecular targeted therapies, PD-(L)1 inhibitors