Efficacy and safety of transarterial therapy combined with donafenib plus PD-1 inhibitors for unresectable hepatocellular carcinoma: A multicenter retrospective study.

Abstract

e16171 Background: Triple therapy combining transarterial therapy, tyrosine kinase inhibitors (TKIs), and programmed death-1 (PD-1) inhibitors represents a promising therapeutic strategy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy combined with donafenib (a TKI) and PD-1 inhibitors as first-line treatment in a real-world uHCC cohort. Methods: This was a multicenter, retrospective study conducted across five medical centers in China. We analyzed patients diagnosed with uHCC who had received at least one cycle of triple combination therapy comprising transarterial therapy (hepatic arterial infusion chemotherapy [HAIC] and/or transarterial chemoembolization [TACE]), donafenib, and PD-1 inhibitors. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgical conversion rate, and safety. Tumor responses were assessed according to both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1. Results: After screening, 70 patients were included in the analysis. Key baseline characteristics were as follows: median age 55 years; 92.9% male; 87.1% with HBV infection; 60.0% at BCLC stage C. Additionally, 48.6% of patients had macrovascular invasion, 22.9% had extrahepatic metastasis, and 74.2% presented with multiple tumors, with a median maximum tumor diameter of 86.5 mm. The PD-1 inhibitors administered included tislelizumab (41.4%), camrelizumab (37.1%), sintilimab (18.6%), toripalimab (2.9%). Transarterial therapy regimens consisted of TACE plus HAIC (38.6%), HAIC alone (34.3%), and TACE alone (27.1%). After a median follow-up of 27.5 months, the median PFS was 12.7 months (95% CI, 8.4-23.8) per both mRECIST and RECIST v1.1. The median OS was 29.3 months (95% CI, 22.4-NA) with 12- and 24-month OS rates of 81.7% and 57.2%, respectively. The ORR was 67.1% per mRECIST and 52.9% per RECIST v1.1, and the DCR was 87.1% by both criteria. The surgical conversion rate was 22.9%. Treatment-related adverse events (TRAEs) occurred in 87.1% of patients, with grade 3-4 events in 37.1%. The most common TRAEs included liver dysfunction (51.4%), hand-foot skin reaction (47.1%), decreased platelet count (18.6%), and decreased white blood cell count (17.1%). Conclusions: This real-world study demonstrates that transarterial therapy combined with donafenib and PD-1 inhibitors provides encouraging survival outcomes and a manageable safety profile for uHCC patients. Clinical trial information: ChiCTR2200063822.