Network meta-analysis suggests immune checkpoint inhibitor regimens improve survival in advanced gastric cancer compared to chemotherapy alone

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Journal of gastrointestinal cancer Published May 24, 2026 Medically reviewed May 24, 2026 Study authors: Zhang Di, Hu Jin, Xu Qian, Jiao Jianqiao, Hu Qinqin, Jiang Fan, Ma Mingchi, Xia Beian, Li Song, Liu … PubMed ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider that dual-target ICI regimens may offer survival benefit but await head-to-head trial confirmation.

This network meta-analysis assessed the efficacy of immune checkpoint inhibitor-based regimens as first-line treatment for advanced gastric cancer. The study compared various combination strategies against chemotherapy alone to determine their impact on overall survival and progression-free survival.

The results indicated that dual-target inhibitor combinations generally provided superior overall survival compared to chemotherapy or single-agent strategies. Specifically, one particular dual-target regimen achieved the most favorable outcomes among the groups analyzed. In contrast, no significant differences were observed among the single-agent inhibitor combinations when compared to each other.

Subgroup analyses revealed that specific regimens performed best in patients with higher tumor expression levels, while dual-target strategies still showed benefit in those with lower expression. The authors note that no inhibitor-based strategy demonstrated benefit in the lowest expression subgroup. Key limitations include the reliance on indirect evidence rather than direct head-to-head comparisons. Future studies should address outcomes in patients with the lowest expression levels.

These findings support personalized therapy selection but must be interpreted with caution. The certainty of the evidence is currently limited by the lack of direct trial data. Clinicians should recognize that practice recommendations await confirmation by head-to-head trials.

Study Details

Study typeMeta analysis

Sample sizen = 8,999

EvidenceLevel 1

PublishedMay 2026

PMID42176095

View Original 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.