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Esophageal Cancer Research and Treatment / Gastric Cancer Management and Outcomes · Review
Frontiers in Oncology · September 9, 2026
Well-designed and adequately powered for the question it asks.
This meta-analysis demonstrates that first-line PD-1/PD-L1 inhibitor plus chemotherapy consistently improves overall and progression-free survival and objective response rate in advanced gastric or gastroesophageal junction cancer compared to chemotherapy alone, but increases grade ≥3 adverse events (RR 1.15), serious adverse events (RR 1.53), and treatment discontinuation (RR 1.53). Treatment-related mortality was imprecisely estimated (RR 1.54, 95% CI 0.75–3.16), precluding definitive conclusions on this endpoint.
Systematic review and meta-analysis of randomized controlled trials. Adults with previously untreated unresectable, recurrent, locally advanced, or metastatic gastric or gastroesophageal junction cancer across 7 RCTs.. Intervention: PD-1/PD-L1 inhibitor plus chemotherapy (first-line).. Compared with: Chemotherapy alone or placebo plus chemotherapy.. n = 6,517. Not specified by region; subgroup analyses performed for global trials versus Asia-only or China-only trials..
Objective response rate increased with combination therapy (RR 1.24; 95% CI 1.18–1.31) with negligible heterogeneity (I² = 0.0%) Overall survival benefit similar in global trials (HR 0.79; 95% CI 0.75–0.85) and Asia-only or China-only trials (HR 0.81; 95% CI 0.73–0.91) Progression-free survival effect greater in Asian-only or China-only trials (HR 0.66 vs. 0.78; P for subgroup difference = 0.02), exploratory analysis
Treatment-related mortality was imprecisely estimated with a wide confidence interval (0.75–3.16) that could not exclude clinically important increases or decreases. Individual trial characteristics and definitions of adverse events are not detailed; source provides only pooled estimates.
Clinicians should consider first-line chemoimmunotherapy for appropriately selected patients with advanced gastric or gastroesophageal junction cancer, recognising consistent survival gains but balancing against increased serious adverse events and treatment discontinuation. Patient fitness, biomarker status, and individual toxicity risk should guide treatment decisions.
A high-quality meta-analysis of 7 RCTs with 6,517 patients showing consistent survival and response benefit for chemoimmunotherapy, but with quantified and clinically relevant toxicity trade-offs that require individualised patient selection.
As stated by the source record.
Quoted from the source exactly as published.
Clinicians should consider first-line chemoimmunotherapy for appropriately selected patients with advanced gastric or gastroesophageal junction cancer, recognising consistent survival gains but balancing against increased serious adverse events and treatment discontinuation. Patient fitness, biomarker status, and individual toxicity risk should guide treatment decisions.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background First-line chemoimmunotherapy has become a major therapeutic strategy for advanced gastric and gastroesophageal junction cancer, yet the magnitude of survival benefit, regional consistency, and toxicity trade-offs remain important considerations. We conducted an systematic review and meta-analysis of randomized controlled trials evaluating PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone or placebo plus chemotherapy. Methods PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov were searched from inception to March 1, 2026. Eligible studies enrolled adults with previously untreated unresectable, recurrent, locally advanced, or metastatic gastric or gastroesophageal junction cancer. Hazard ratios were pooled for overall survival and progression-free survival, and risk ratios were pooled for objective response rate and safety outcomes using random-effects models. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE. Results Seven randomized controlled trials including 6,517 patients were analyzed. PD-1/PD-L1 inhibitor plus chemotherapy significantly improved overall survival and progression-free survival. Objective response rate was also increased (RR, 1.24; 95% CI, 1.18–1.31), with negligible observed heterogeneity (I² = 0.0%). Overall survival effects were similar in global trials (HR, 0.79; 95% CI, 0.75–0.85) and Asian-only or China-only trials (HR, 0.81; 95% CI, 0.73–0.91; P for subgroup difference = 0.70). The progression-free survival effect was greater in Asian-only or China-only trials (HR, 0.66 vs. 0.78; P for subgroup difference = 0.02), although this analysis was exploratory. Combination therapy increased grade ≥3 treatment-related adverse events (RR, 1.15; 95% CI, 1.08–1.23), serious treatment-related adverse events (RR, 1.53; 95% CI, 1.29–1.83), and treatment discontinuation (RR, 1.53; 95% CI, 1.37–1.72). The pooled estimate for treatment-related death was statistically inconclusive (RR, 1.54; 95% CI, 0.75–3.16); the wide confidence interval indicated substantial imprecision and could not exclude clinically important increases or decreases in treatment-related mortality. Conclusions First-line PD-1/PD-L1 inhibitor + chemotherapy provides a consistent survival and response benefit in advanced gastroesophageal junction or gastric cancer, but with increased clinically relevant toxicity. These findings support chemoimmunotherapy as a preferred first-line strategy for appropriately selected patients, with treatment decisions guided by biomarker status, patient fitness, and toxicity risk.
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