Optimal First-line Immune-related Therapy Selection for Advanced Gastric Cancer: A Systematic Review and Network Meta-analysis

Clinical Snapshot

Key Findings

• P Value: Significant survival benefits reported but specific p-values not provided

• Effect Size: Dual-target ICI-chemo superior to dual ICIs±chemo and single ICI±chemo (specific measures not provided in abstract)

• Primary Outcome: Overall survival and progression-free survival significantly improved with dual-target ICI-chemo compared to other strategies

• Nnt Or Sensitivity: Cadon-chemo most effective in PD-L1 CPS ≥ 10 and CPS ≥ 1 subgroups

• Confidence Interval: Not reported in abstract

Clinical Application

Requires PD-L1 testing and access to dual-target immunotherapy combinations Relevant to Australian practice where pembrolizumab combinations are PBS-listed for gastric cancer; findings may inform TGA submissions for newer dual-target agents Patients with advanced gastric cancer suitable for first-line systemic therapy, particularly those with PD-L1 CPS ≥ 1

Abstract

PURPOSE: Although immune checkpoint inhibitors combined with chemotherapy improve survival in advanced gastric cancer (AGC), comparative evidence across first-line regimens remains insufficient. This study aimed to systematically evaluate their relative efficacy and safety. METHODS: PubMed, Embase, the Cochrane Library, Web of Science, and major conferences were searched up to February 28, 2025. Eligible RCTs comparing ICI-related regimens as first-line AGC treatment were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: Eleven RCTs involving 8,999 patients, six integrated strategies, and twelve specific regimens were included. Dual-target ICI-chemo and single ICI-chemo showed significant survival benefits over chemotherapy, whereas dual ICIs±chemo and single ICI alone did not. Dual-target ICI-chemo was associated with significantly better survival than both dual ICIs±chemo and single ICI±chemo. Among the specific regimens, cadon-chemo achieved the most favorable OS and PFS. No significant OS differences were observed among the single ICI-chemo regimens. In PD-L1-positive subgroups, both dual-target ICI-chemo and single ICI-chemo significantly improved survival compared with chemotherapy, with cadon-chemo being most effective in CPS ≥ 10 and CPS ≥ 1, and SHR1701-chemo in CPS ≥ 5. In the CPS < 5 subgroup, dual-target ICI-chemo significantly improved OS, while single ICI-chemo showed a trend toward benefit. However, no ICI-based strategy demonstrated benefit in CPS < 1. CONCLUSIONS: Dual-target ICI-chemo appears to be the most effective first-line strategy for AGC based on current indirect evidence, surpassing single ICI-chemo and dual ICI-based regimens. These findings support personalized therapy selection but await confirmation by head‑to‑head trials. Future studies should address CPS < 1 and explore optimized combinations to enhance outcomes.

References

1. 1.Zhang, D., Hu, J., Xu, Q., Jiao, J., Hu, Q., Jiang, F., Ma, M., Xia, B., Li, S., & Liu, L. (2026). Optimal First-line Immune-related Therapy Selection for Advanced Gastric Cancer: A Systematic Review and Network Meta-analysis. Journal of Gastrointestinal Cancer. https://doi.org/10.1136/annrheumdis-2016-209595