Immunotherapy has become a foundational component of first-line management for advanced gastric and gastroesophageal junction cancer (G/GEJC). After disease progression on such regimens, however, the optimal second-line approach remains uncertain. Because cadonilimab has demonstrated strong activity in initial treatment, this real-world analysis explored its use with chemotherapy in the second-line setting. We performed a retrospective review at a single institution involving patients with advanced G/GEJC who experienced progression following first-line immunotherapy. From October 2022 to April 2025, patients received either cadonilimab plus chemotherapy (Cohort A, n=50) or chemotherapy alone (Cohort B, n=62). The main outcome was overall survival (OS). Secondary measures consisted of progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Cohort A demonstrated noticeably better clinical performance. Median PFS reached 4.9 months (95% CI: 3.9–6.0) compared with 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) versus 7.4 months (95% CI: 6.9–7.9) (p=0.046). ORR was 34.0% vs 17.7% (p=0.048), and DCR was 74.0% vs 54.8% (p=0.036). Adverse-event frequencies were comparable, and no deaths were attributed to treatment. Relative to chemotherapy alone, the combination of cadonilimab and chemotherapy yielded superior outcomes with manageable toxicity in patients who progressed after first-line immunotherapy. These observations suggest that cadonilimab-based regimens could serve as a promising second-line option. Prospective randomized trials will be necessary to verify these results.
