Efficacy hierarchy and absolute survival benefit of first-line immunotherapy in advanced gastric cancer: a meta-analysis and pooled survival analysis
In brief
Immunotherapy plus chemo adds about two months overall survival in advanced gastric cancer
A meta-analysis of eight phase III trials (7,127 patients) showed that first-line immune checkpoint inhibitor combined with chemotherapy extended median overall survival to 14.4 months versus 12.6 months with chemotherapy alone, and improved progression-free survival similarly. Benefit grew with higher PD-L1 expression, while severe toxicities rose only modestly, supporting immunochemotherapy as a viable first-line option.
- Journal
- Frontiers in immunology (Q1)
- Published
- 17 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Jialun Lv, Krishnapriya Thangaretnam, Md Obaidul Islam, Jason Tang, Sabine Denize, Nadeem Bhat, et al.
- PMID
- 42676632
- DOI
- 10.3389/fimmu.2026.1866848
Why clinicians should know about it
- Picked for Pharmacology (medical) (top studies of the week, 6 September 2026): Meta‑analysis of immunotherapy, no PK focus
- Picked for Oncology and Radiation Oncology (top studies of the week, 6 September 2026): Meta‑analysis of ICI‑chemo in advanced gastric cancer
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.