TACE-HAlC combined with Donafenib and immune checkpoint inhibitors for BCLC stage C HCC patients (THEME study): a...

Treatment options for Barcelona Clinic Liver Cancer (BCLC) Stage C hepatocellular carcinoma (HCC) remain limited, with targeted therapy combined with immune checkpoint inhibitors (ICIs) serving as the standard first-line treatment. This study investigates whether a combination of transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), donafenib, and ICIs (quadruple therapy) provides superior survival benefits compared to the targeted therapy combined with ICIs (targeted-immunotherapy).

We conducted a retrospective analysis of patients with BCLC stage C HCC who received quadruple therapy or targeted-immunotherapy at the Harbin Medical University Cancer Hospital between September 2019 and October 2024The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), Disease Control Rate (DCR) and safety. To minimize baseline imbalances between the groups, we applied stabilized inverse probability of treatment weighting (sIPTW) methods.

A total of 195 patients were included in the study, of whom 125 were assigned to the quadruple therapy group and 70 to the targeted-immunotherapy Group. After applying sIPTW to balance the baseline characteristics between the two groups, patients in the quadruple therapy group demonstrated a significantly higher median OS (mOS) compared with the targeted-immunotherapy group (29.4 months [95% CI: 23.9-NA] vs 18.0 months [14.7-31.8]; P = 0.041). Additionally, the median PFS (mPFS) assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was longer in the quadruple therapy group(16.4 months [95% CI: 12.7-NA] vs 10.0 months [3.32-31.8]; P = 0.012). Under the mRECIST criteria, quadruple therapy group demonstrated superior)ORR (68.4% vs 28.%, P = 0.001) and DCR (92.3% vs 63.1%, P < 0.001). The incidence of any adverse events (AE) in the quadruple therapy group was 95.2%, compared with 97.1% in the targeted-immunotherapy group. Among these the incidence of grade ≥3 AE was 40.8% in the quadruple therapy group and 38.6% in the targeted-immunotherapy group.

Compared with targeted-immunotherapy group, patients with BCLC stage C HCC treated with TACE-HAIC combined with donafenib and ICIs demonstrated superior efficacy and acceptable safety.