Abstract
OBJECTIVE: This study retrospectively evaluated the safety and efficacy of cadonilimab combined with tyrosine kinase inhibitors (TKI) for the treatment of unresectable hepatocellular carcinoma (uHCC). PATIENTS AND METHODS: Seventy-eight patients who received cadonilimab + TKI were included; 42 and 36 received it as first-line (1 L) and second-line and above (≥ 2 L) systemic treatment, respectively. Besides, ninety-five patients who received PD-1 inhibitor + TKI as first-line treatments were included. Safety was the primary endpoint; secondary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). RESULTS: Treatment-related adverse events (TRAEs) of any grade occurred in 84.6% of the patients, with grade ≥ 3 in 20.5%. In patients with a Child-Pugh score of ≥ 8 (CP ≥ 8), any grade TRAEs occurred in 88.2%, and grade ≥ 3 in 20.6%. The overall cohort's median progression-free survival (mPFS) was 3.6 months, whereas the median overall survival (mOS) was 8.8 months. In the 1 L group, mPFS was 6.7 months versus 2.3 months in ≥ 2 L. In the 1 L group, mOS was 13.7 months versus 3.2 months in ≥ 2 L. For CP < 8, 1 L mPFS was 7.6 months, mOS not reached; CP ≥ 8 had mPFS of 5.2 months, mOS of 5.6 months. For CP < 8 in ≥ 2 L, mPFS was 3.1 months, mOS 8.8 months; CP ≥ 8 had mPFS of 1.4 months, mOS of 2.2 months. After propensity score matching (PSM), the incidence of TRAEs of any grade was 77.1%, with grade ≥ 3 accounting for 17.1% in the PD-1 group. In the PD-1/CTLA-4 group, the incidence of TRAEs of any grade was 80.0%, and that of grade ≥ 3 TRAEs was 17.1%. The mPFS was 6.7 months in the PD-1/CTLA-4 group versus 3.3 months in the PD-1 group. The mOS was 13.7 months in the PD-1/CTLA-4 group versus 6.7 months in the PD-1 group. CONCLUSION: Cadonilimab + TKI showed a favorable trend in safety and efficacy, especially when applied as first-line systemic therapy for uHCC. This study offers a clinical reference for its use in systemic uHCC therapy, particularly in patients with advanced liver dysfunction.