Abstract
BACKGROUND: Cadonilimab (AK104) is a first-in-class bispecific antibody targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). This study evaluated the effectiveness and safety of cadonilimab plus chemotherapy vs. PD-1 inhibitor plus chemotherapy as first-line treatment for advanced gastric/gastroesophageal junction (G/GEJ) cancer with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) <5. METHODS: Between August 2022 and August 2024, patients with PD-L1 CPS <5 G/GEJ cancer who received first-line cadonilimab plus chemotherapy (cadonilimab group) or PD-1 inhibitor plus chemotherapy (PD-1 inhibitor group) were included. After propensity score matching (PSM), the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety were analyzed. RESULTS: Fifty-two patients were analyzed after PSM (26 per group). At data cutoff (February 28, 2025), median follow-up was 11.0 months [95% confidence interval (CI): 8.3-15.3]. Compared with the PD-1 inhibitor group, cadonilimab group exhibited a numerically higher ORR (73.3% vs. 57.1%, P=0.45). In addition, the median PFS [9.3 vs. 5.8 months; hazard ratio (HR) =0.43; 95% CI: 0.23-0.80; P=0.006] and OS (14.3 vs. 10.3 months; HR =0.49; 95% CI: 0.26-0.93; P=0.03) were significantly longer in the cadonilimab group than in the PD-1 inhibitor group. The incidence of treatment-related adverse events (AEs) was comparable between the two groups, occurring in 92.3% of patients receiving cadonilimab plus chemotherapy and 100.0% of those receiving PD-1 inhibitor plus chemotherapy. Immune-related AEs occurred in 8 patients (30.8%) in the cadonilimab group and 6 patients (23.1%) in the PD-1 inhibitor group. CONCLUSIONS: Compared to PD-1 inhibitor plus chemotherapy, cadonilimab plus chemotherapy significantly improved PFS and OS with a manageable safety profile in the first-line treatment of advanced G/GEJ cancer with PD-L1 CPS <5 in a real-world setting.