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Gastrointestinal Tumor Research and Treatment / Gastric Cancer Management and Outcomes · Review
Frontiers in Immunology · August 17, 2026
Well-designed and adequately powered for the question it asks.
This meta-analysis of 8 phase III trials demonstrates that first-line ICI-chemotherapy significantly improves overall survival and progression-free survival compared to chemotherapy alone in advanced gastric and gastroesophageal junction adenocarcinoma, with survival benefit correlating to PD-L1 expression level. The absolute median OS benefit is 1.8 months and PFS benefit is 1.1 months, achieved with a modest increase in grade ≥3 adverse events.
Systematic review and meta-analysis of phase III randomized controlled trials. Eight phase III trials enrolling previously untreated, HER2-negative patients with advanced gastric or gastroesophageal junction adenocarcinoma. Intervention: Immune checkpoint inhibitor plus chemotherapy. Compared with: Chemotherapy alone. n = 7,127.
Pooled OS hazard ratio 0.79 (95% CI not reported) favoring ICI-chemotherapy, with median OS of 14.4 months versus 12.6 months with chemotherapy alone Pooled PFS hazard ratio 0.71 (95% CI not reported) with median PFS of 7.3 months versus 6.2 months OS benefit increased with higher PD-L1 CPS: HR 0.90 (CPS 1), 0.76 (CPS ≥1), 0.74 (CPS ≥5), and 0.65 (CPS ≥10)
Absolute numbers of adverse events and their severity grades not detailed Grade ≥3 adverse events risk ratio 1.16 and serious adverse events risk ratio 1.54 with combination therapy
These results support the use of first-line ICI-chemotherapy as standard treatment for advanced gastric cancer, with treatment selection refined by PD-L1 expression levels. Clinicians should counsel patients on the modest but consistent survival benefit (1.8 months median OS gain) balanced against increased toxicity.
High-quality meta-analysis of 8 phase III RCTs with 7,127 patients showing consistent, statistically significant OS and PFS benefit for ICI-chemotherapy over chemotherapy alone in advanced gastric cancer, with clinically meaningful absolute survival gains and manageable toxicity.
As stated by the source record.
Quoted from the source exactly as published.
These results support the use of first-line ICI-chemotherapy as standard treatment for advanced gastric cancer, with treatment selection refined by PD-L1 expression levels. Clinicians should counsel patients on the modest but consistent survival benefit (1.8 months median OS gain) balanced against increased toxicity.
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 While immune checkpoint inhibitors (ICIs) have revolutionized first-line treatment for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, outcomes across phase III trials remained heterogeneous. This study aimed to determine the efficacy and safety of ICI plus chemotherapy, and to define a clinically meaningful PD-L1 expression threshold through a meta-analysis. Methods We systematically searched PubMed, Embase, and Cochrane for phase III randomized controlled trials (up to November 2025) comparing ICI-chemotherapy combinations against chemotherapy alone in patients with advanced gastric or GEJ adenocarcinoma. The combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using a random-effects model. Safety was assessed through the combined risk ratio (RR) of grade ≥3 adverse events (AEs) and serious adverse events (SAEs). Results Eight trials involving 7,127 patients with previously untreated, HER2-negative, advanced gastric or GEJ adenocarcinoma were included. The pooled analysis showed a significant improvement in OS (HR = 0.79) and PFS (HR = 0.71) with immunochemotherapy versus chemotherapy alone. Immunochemotherapy was associated with longer median OS (14.4 vs 12.6 months) and PFS (7.3 vs 6.2 months). Treatment benefit increased with higher PD-L1 combined positive score (CPS): OS HRs were 0.90 (CPS 1), 0.76 (CPS ≥ 1), 0.74 (CPS ≥ 5), and 0.65 (CPS ≥ 10). Combination therapy modestly increased grade ≥3 AEs (RR = 1.16) and SAEs (RR = 1.54) compared with chemotherapy alone. Conclusions Our results supported the strategy of first-line immunochemotherapy, which significantly prolongs OS and PFS in advanced gastric and GEJ adenocarcinoma with manageable toxicity. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251180445, identifier CRD420251180445.
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