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Background <p>The optimal first-line immunotherapy- or targeted therapy-based regimen for advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC) remains uncertain, largely because direct head-to-head comparisons are limited. We therefore conducted a network meta-analysis to compare the efficacy and safety of currently available first-line treatment strategies.</p> Methods <p>PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched from inception to January 10, 2026, for randomized controlled trials evaluating first-line immunotherapy- or targeted therapy-based regimens for advanced GC or GEJC. Overall survival (OS) and progression-free survival (PFS) were analyzed using hazard ratios (HRs), and dichotomous outcomes were analyzed using odds ratios (ORs), both with 95% credible intervals (CrIs). Risk of bias was assessed using the Cochrane RoB 2 tool. Bayesian network meta-analysis performs by R4.3.1.</p> Results <p>Nineteen randomized controlled trials involving 10,808 patients were included. No statistically significant differences were observed among treatment regimens for OS or PFS. Several immunotherapy- and targeted therapy-based regimens demonstrated improvements in short-term tumor response outcomes, including ORR and DCR; however, these improvements were not consistently associated with survival benefits. SUCRA-based ranking results suggested variability in probabilistic treatment ordering but should be interpreted as exploratory rather than definitive evidence of clinical superiority. Substantial clinical and methodological heterogeneity was observed across trials, including differences in biomarker status (PD-L1, HER2, CLDN18.2, FGFR2b), geographic regions, chemotherapy backbones, and subsequent treatment strategies. In safety analyses, EGFR-targeted agents showed relatively favorable profiles in selected outcomes.</p> Conclusions <p>Although certain regimens were associated with improved short-term tumor responses, there is insufficient evidence to support definitive superiority in terms of long-term survival outcomes. Given biomarker heterogeneity, clinical variability, and limitations in network structure, these findings should be interpreted cautiously. Further biomarker-stratified and head-to-head randomized trials are warranted to better define optimal treatment strategies.</p>

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Comparative efficacy and safety of first-line immunotherapy- and targeted therapy-based regimens for advanced gastric and gastroesophageal junction cancer: a network meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月6日

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  • Wanting Wang,
  • Xiaoning Zhang,
  • Xiaohu Sun,
  • Lu Wang

摘要

Background

The optimal first-line immunotherapy- or targeted therapy-based regimen for advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC) remains uncertain, largely because direct head-to-head comparisons are limited. We therefore conducted a network meta-analysis to compare the efficacy and safety of currently available first-line treatment strategies.

Methods

PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched from inception to January 10, 2026, for randomized controlled trials evaluating first-line immunotherapy- or targeted therapy-based regimens for advanced GC or GEJC. Overall survival (OS) and progression-free survival (PFS) were analyzed using hazard ratios (HRs), and dichotomous outcomes were analyzed using odds ratios (ORs), both with 95% credible intervals (CrIs). Risk of bias was assessed using the Cochrane RoB 2 tool. Bayesian network meta-analysis performs by R4.3.1.

Results

Nineteen randomized controlled trials involving 10,808 patients were included. No statistically significant differences were observed among treatment regimens for OS or PFS. Several immunotherapy- and targeted therapy-based regimens demonstrated improvements in short-term tumor response outcomes, including ORR and DCR; however, these improvements were not consistently associated with survival benefits. SUCRA-based ranking results suggested variability in probabilistic treatment ordering but should be interpreted as exploratory rather than definitive evidence of clinical superiority. Substantial clinical and methodological heterogeneity was observed across trials, including differences in biomarker status (PD-L1, HER2, CLDN18.2, FGFR2b), geographic regions, chemotherapy backbones, and subsequent treatment strategies. In safety analyses, EGFR-targeted agents showed relatively favorable profiles in selected outcomes.

Conclusions

Although certain regimens were associated with improved short-term tumor responses, there is insufficient evidence to support definitive superiority in terms of long-term survival outcomes. Given biomarker heterogeneity, clinical variability, and limitations in network structure, these findings should be interpreted cautiously. Further biomarker-stratified and head-to-head randomized trials are warranted to better define optimal treatment strategies.