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Timing of Immune Checkpoint Inhibitor Initiation and Overall Survival in Advanced Gastric Cancer: A Multicenter
Shota Shimizu1, Tomoyuki Matsunaga2, Sadamu Takahashi3
1Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan. s.shimizu@tottori-u.ac.jp.
Journal of Gastrointestinal Cancer
|August 13, 2026
Summary
Optimal timing for immune checkpoint inhibitors (ICIs) in advanced gastric cancer (GC) did not impact survival, though ICI use improved tumor response. This suggests a disconnect between short-term response and long-term outcomes in GC patients.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Cancers
Background:
- Immune checkpoint inhibitors (ICIs) are a cornerstone in advanced gastric cancer (GC) treatment.
- The optimal timing for initiating ICIs in GC remains an area of active investigation.
- Real-world data is crucial for understanding the impact of ICI timing on clinical outcomes.
Purpose of the Study:
- To evaluate the association between the timing of immune checkpoint inhibitor (ICI) initiation and survival outcomes in advanced gastric cancer (GC).
- To assess the impact of ICI initiation timing on tumor response in patients with advanced GC.
- To provide real-world evidence on the clinical utility of ICI timing in GC management.
Main Methods:
- A multicenter retrospective study involving unresectable or recurrent GC patients treated with first-line chemotherapy.
- Application of a clone-censor-weight (CCW) approach to mitigate immortal time bias in overall survival (OS) analysis for patients receiving ICIs.
- Logistic regression analysis to identify factors associated with tumor response in patients treated with standard chemotherapy regimens (SOX or CapeOX).
Main Results:
- The timing of ICI initiation was not significantly associated with overall survival (OS) in advanced GC patients (HR 1.03, 95% CI 0.71-1.51).
- The addition of ICIs significantly improved the objective response rate (ORR) compared to chemotherapy alone (56.3% vs. 34.2%, P=0.017).
- ICI use was independently associated with improved tumor response (OR 2.31, 95% CI 1.07-5.01, P=0.034).
Conclusions:
- In a real-world cohort of advanced GC patients, ICI initiation timing did not correlate with survival outcomes.
- Despite no survival benefit related to timing, ICI-containing regimens demonstrated improved tumor response.
- These findings highlight a potential discordance between short-term tumor response and long-term survival in advanced GC treated with ICIs.
