Post-Progression Immunotherapy and Prognostic Factors in HER2-Negative Advanced Gastric Cancer: A Retrospective Analysis of 118 Cases

Purpose: Advanced gastric cancer (AGC) has a poor prognosis, and optimal management post-progression on immune checkpoint inhibitors (ICIs) remains undefined. This study evaluates survival outcomes of continuing ICIs beyond progression in HER2-negative AGC, focusing on progression patterns and biomarker correlates. Methods: A retrospective cohort of HER2-negative AGC patients treated with ICIs at Anhui Provincial Hospital (2018–2022) was analyzed. Eligible patients (n=118) had ≥3 months of stable disease before progression. Primary endpoints included progression-free survival (PFS1, PFS2) and overall survival (OS). Kaplan-Meier analysis, Cox regression, and biomarker assessments (neutrophil-to-lymphocyte ratio [NLR], Systemic Immune-Inflammation Index [SII]) were performed. Results: Median PFS1 was 6.8 months. Patients continuing ICIs post-progression (CIBP group) demonstrated significantly improved PFS2 (12.9 vs. 11.2 months, p=0.020) and OS (19.0 vs. 13.5 months, p=0.019) compared to discontinuers (DIBP). Systemic progression (SP) was predominant; patients with acquired resistance (ICI exposure >6 months) and systemic progression derived the greatest benefit from CIBP. Elevated NLR/SII predicted reduced post-progression efficacy. Conclusion: Continuing ICIs post-progression improves survival in HER2-negative AGC, particularly for SP with acquired resistance. Progression patterns and NLR/SII may guide clinical decisions. Prospective trials integrating dynamic biomarker monitoring are warranted to validate rechallenge strategies. retrospectively registered： IRB approval number:2025-XZY-01