Abstract
BACKGROUND: Transcatheter arterial chemoembolization (TACE) is widely used for intermediate-advanced hepatocellular carcinoma (HCC). The efficacy and safety of TACE combined with systemic treatments as conversion therapy for HCC remain to be explored. METHODS: Patients with intermediate-advanced HCC were divided as following groups based on therapy: (1) TACE; (2) TACE combined with tyrosine kinase inhibitors (TACE+TKI); (3) TACE+TKI and immune checkpoint inhibitors (TACE+TKI+ICI); and (4) TACE combined with Bevacizumab and ICI. The progression-free survival (PFS), overall survival (OS), treatment responses, and adverse events (AEs) were evaluated. RESULTS: Of the enrolled 518 patients, the overall objective response rate (ORR) was 21.0% and disease control rate (DCR) was 63.7%, while the TACE+TKI+ICI group showed highest ORR (28.9%) and DCR (72.8%). 147 (28.4%) patients experienced AEs during treatments. The TACE+TKI+ICI group significantly improved survival compared to TACE (mPFS: 20.7 vs. 10.9 months, p < 0.001; mOS: 44.0 vs. 13.3 months, p < 0.001) or TACE+TKI (mPFS: 20.7 vs. 15.6 months, p = 0.011; mOS: 44.0 vs. 25.0 months, p < 0.001). Of the 117 (22.6%) patients who underwent conversion liver resection, both mPFS (p = 0.016) and mOS (p < 0.001) were significantly better than those without subsequent resection. DISCUSSION: This study demonstrated that TACE+TKI+ICI had a better ORR, manageable AEs, and superior PFS and OS compared to other TACE-based conversion therapies. Undergoing subsequent liver resection significantly enhanced long-term survival compared to non-resection counterparts.