Efficacy of anti-PD-1/PD-L1 plus chemotherapy in treatment-naïve advanced HER2-negative gastric adenocarcinoma among different PD-L1 intervals: an updated meta-analysis and reconstructed individual patient-level data analysis
In brief
Immunotherapy plus chemotherapy cuts death risk 33% in high-score gastric cancer
In a pooled analysis of randomized trials, adding a PD-1 or PD-L1 inhibitor to chemotherapy lowered the risk of death by 33% for patients with advanced HER2-negative gastric or gastroesophageal junction cancer whose tumor score was 10 or higher. Overall survival benefit was not clear at lower scores, though progression-free survival and response rates improved in some groups; the strongest evidence supports the 10-or-higher threshold.
- Journal
- BMC medicine (Q1)
- Published
- 8 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Yu-Kun Chen, Wen-Wei Wu, Fan Chen, Lan-Jie Chen, Hao-Xiang Wu, Ying-Nan Wang, et al.
- PMID
- 42983403
- DOI
- 10.1186/s12916-026-05124-z
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 6 November 2026): Meta-analysis informs PD-L1-guided gastric chemo-immunotherapy
Abstract
BACKGROUND: Chemo-immunotherapy (CIT) has become the frontline therapy for advanced human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-esophageal junction adenocarcinoma (GEAC). However, emerging evidence suggests that clinical benefit is primarily derived from patients with a high combined positive score (CPS), whereas the efficacy of CIT among different CPS intervals remained unknown. METHODS: A systemic literature search was performed to screen for RCTs studying addition of PD-1/PD-L1 inhibitors to chemotherapy versus chemotherapy alone in metastatic GEAC with efficacy information across different CPS interval. Pooled analysis of hazard ratios (HRs) for overall survival (OS), progression free survival (PFS), odds ratios (ORs) for objective response rate (ORR) and heterogeneity analysis on treatment efficacy were performed in CPS < 1, 1 ~ 4, 5 ~ 9, ≥10 subgroups. RESULTS: The analysis showed that adding programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors to ChT significantly improved overall survival (OS) in the CPS ≥ 10 subgroup (hazard ratio [HR], 0.67 [95%CI 0.61-0.73]), but not in the CPS < 1 or 5-9 subgroups; only a marginal benefit was observed in the CPS 1-4 subgroup. CPS ≥ 10 vs <10 presented the strongest interaction effect between CPS and the efficacy of adding PD-1/PD-L1 inhibitors to ChT (Pinteraction < 0.0001). Additionally, CIT significantly improved the progression-free survival (PFS) and objective response rate (ORR) in both CPS-low (CPS < 1: HR, 0.85 [95%CI 0.72-1.00]; odds ratio [OR], 1.41 [95%CI 1.02-1.96]) and CPS-high (CPS ≥ 10: HR, 0.64 [95%CI 0.58-0.70]; OR, 1.87 [95%CI 1.50-2.33]) subgroups versus ChT alone. CONCLUSIONS: CPS ≥ 10 defines a subgroup deriving the greatest benefit from CIT, supporting its use as a clinically informative threshold for PD-1 inhibitor therapy in advanced GEAC. Nevertheless, patients with CPS < 10 may still gain benefit from CIT when tumor shrinkage is the primary treatment objective.
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.