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Optimal First-line Immune-related Therapy Selection for Advanced Gastric Cancer: A Systematic Review and Network
1Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Journal of Gastrointestinal Cancer
|May 23, 2026
Summary
Dual-target immune checkpoint inhibitor (ICI) plus chemotherapy is the most effective first-line treatment for advanced gastric cancer (AGC), improving survival compared to other ICI regimens. Further research is needed for patients with low PD-L1 expression.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Oncology
Background:
- First-line treatment with immune checkpoint inhibitors (ICIs) combined with chemotherapy has improved survival in advanced gastric cancer (AGC).
- Comparative evidence across different first-line ICI-based regimens is limited, necessitating systematic evaluation.
Purpose of the Study:
- To systematically evaluate the relative efficacy and safety of various first-line immune checkpoint inhibitor (ICI)-based regimens for advanced gastric cancer (AGC).
- To compare dual-target ICI-chemotherapy, single ICI-chemotherapy, dual ICIs±chemotherapy, and single ICI monotherapy.
Main Methods:
- A systematic literature search was conducted across major databases (PubMed, Embase, Cochrane Library, Web of Science) and conference proceedings up to February 28, 2025.
- Included were randomized controlled trials (RCTs) comparing first-line ICI-related regimens for AGC treatment.
- Primary outcomes assessed were overall survival (OS) and progression-free survival (PFS).
Main Results:
- Eleven RCTs involving 8,999 patients were analyzed, evaluating six integrated strategies and twelve specific regimens.
- Dual-target ICI-chemotherapy and single ICI-chemotherapy significantly improved survival over chemotherapy alone.
- Dual-target ICI-chemotherapy demonstrated superior survival benefits compared to dual ICIs±chemotherapy and single ICI±chemotherapy. Cadon-chemotherapy showed the most favorable OS and PFS. In PD-L1 positive subgroups, dual-target ICI-chemo and single ICI-chemo improved survival, with specific regimens showing efficacy based on CPS scores. Dual-target ICI-chemo improved OS in the CPS<5 subgroup, while no ICI strategy benefited patients with CPS<1.
Conclusions:
- Dual-target ICI-chemotherapy represents the most effective first-line strategy for advanced gastric cancer (AGC) based on current indirect evidence.
- Findings support personalized therapy selection, but head-to-head trials are needed for confirmation.
- Future research should focus on patients with low PD-L1 expression (CPS<1) and explore optimized combination therapies.
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