Real-World Efficacy of Cadonilimab Plus Chemotherapy as Second-Line Therapy in Immunotherapy-Pretreated Advanced HER2 Negative Gastric or Gastroesophageal Junction Cancer

Zeyu Liu,* Yuxiao Lu,* Ming Li, Jinyu Xiang, Ping Sun, Aina Liu Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Sun, Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People’s Republic of China, Email [email protected] Aina Liu, Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People’s Republic of China, Email [email protected]: Immunotherapy is now a cornerstone of first-line treatment for advanced gastric or gastroesophageal junction cancer (G/GEJC). However, optimal second-line options after progression on first-line immunotherapy are undefined. Given the established efficacy of cadonilimab in the first-line setting, this real-world study evaluated its combination with chemotherapy as a second-line treatment.Methods: We conducted a single-center retrospective study of patients with advanced G/GEJC progressing after first-line immunotherapy. Patients received either cadonilimab plus chemotherapy (Cohort A, n=50) or chemotherapy alone (Cohort B, n=62) as second-line therapy between October 2022 and April 2025. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.Results: Cohort A showed significantly improved outcomes. Median PFS was 4.9 months (95% CI: 3.9– 6.0) in Cohort A vs 3.8 months (95% CI: 2.8– 4.8) in Cohort B (p=0.024). Median OS was 10.3 months (95% CI: 8.8– 11.8) vs 7.4 months (95% CI: 6.9– 7.9), respectively (p=0.046). ORR was 34.0% vs 17.7% (p=0.048), and DCR was 74.0% vs 54.8% (p=0.036). Safety was comparable between cohorts, with no treatment-related deaths.Conclusion: Cadonilimab plus chemotherapy significantly improved efficacy outcomes versus chemotherapy alone in patients with advanced G/GEJC after first-line immunotherapy progression, with a manageable safety profile. This suggests cadonilimab based therapy is a promising second-line strategy. Further prospective randomized studies are needed to confirm these findings.Keywords: PD-1/CTLA-4 bispecific, cadonilimab, advanced gastroesophageal junction cancer, second-line treatment, efficacy, safety