Timing of Immune Checkpoint Inhibitor Initiation and Overall Survival in Advanced Gastric Cancer: A Multicenter Real-World Study Using Clone-Censor-Weight Analysis.

PURPOSE: The optimal timing of immune checkpoint inhibitor (ICI) initiation in advanced gastric cancer (GC) remains unclear. In this study, we evaluated the association between ICI initiation timing, tumor response, and survival outcomes in a real-world setting for GC. METHODS: We conducted a multicenter retrospective study of patients with unresectable or recurrent GC who initiated first-line chemotherapy between January 2015 and September 2025. To adjust for immortal time bias, a clone-censor-weight (CCW) approach was applied to evaluate overall survival (OS) among the patients who received ICIs. Tumor response was assessed in patients treated with first-line S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX), with logistic regression analysis performed to identify factors associated with response. RESULTS: A total of 359 GC patients were included, of whom 219 received ICIs and were included in the CCW analysis. The ICI initiation timing was not significantly associated with OS (hazard ratio 1.03, 95% confidence interval (CI) 0.71-1.51, P = 0.88). In contrast, the addition of ICIs significantly improved the objective response rate compared with chemotherapy alone (56.3% vs. 34.2%, P = 0.017). ICI use remained independently associated with an improved response (odds ratio 2.31, 95% CI 1.07-5.01, P = 0.034). CONCLUSIONS: In this real-world GC patient cohort, ICI initiation timing was not associated with survival, despite an improved tumor response with an ICI-containing therapeutic regimen. These findings suggest a potential discordance between short-term response and long-term survival outcomes in advanced GC.