Abstract
BACKGROUND: The combination of tyrosine kinase inhibitors (TKIs) with transarterial chemoembolization (TACE) holds promise for unresectable hepatocellular carcinoma (HCC). This study aimed to directly compare the efficacy and safety of donafenib (Dona)-TACE vs. lenvatinib (LEN)-TACE as first-line therapies. METHODS: In this retrospective study, 93 unresectable HCC patients (49 Dona-TACE, 44 LEN-TACE; 93% hepatitis B virus-infected) treated between October 2020 and May 2023 were analyzed. Patients received TACE (conventional or drug-eluting beads) combined with Dona (200 mg twice daily) or LEN (8-12 mg/day). Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Survival analyses employed Kaplan-Meier and log-rank tests. RESULTS: Median OS (mOS) was 14.00 months (Dona-TACE) vs. 19.00 months (LEN-TACE) [hazard ratio (HR) =1.25; 95% confidence interval (CI): 0.78-1.99; P=0.330]. Median PFS was 7.37 vs. 5.77 months (HR =0.785; 95% CI: 0.46-1.33; P=0.354), with no significant differences. ORR (55.10% vs. 61.36%, P=0.541) and DCR (75.51% vs. 81.82%, P=0.460) were comparable. Dona-TACE showed significantly lower overall AE rates (any grade: 85.71% vs. 100.00%, P=0.013; grade ≥3: 22.45% vs. 45.45%, P=0.027), including reduced hypertension (2.04% vs. 36.36%, P<0.001), diarrhea (6.12% vs. 25.00%, P=0.011), and vomiting (0.00% vs. 40.91%, P<0.001). CONCLUSIONS: Dona-TACE and LEN-TACE demonstrated comparable efficacy in unresectable HCC, but Dona-TACE exhibited a superior safety profile, suggesting its potential as a preferable option for patients with higher comorbidity risks. Further prospective studies are warranted to validate these findings.