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
6 affiliations
- 1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 China
- 2Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060 P. R. China
- 3Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060 China
- 4Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080 China
- 5Department of Clinical Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 China
- 6Faculty of Medical Science, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510630 China
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.
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BibTeX
@article{chen2026efficacy,
title = {{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}},
author = {Yu-Kun Chen and Wen-Wei Wu and Fan Chen and Lan-Jie Chen and Hao-Xiang Wu and Ying-Nan Wang and Ying Jin and Yu-Tong Chen and Zi-Xian Wang},
journal = {BMC Medicine},
year = {2026},
month = aug,
doi = {10.1186/s12916-026-05124-z},
url = {https://doi.org/10.1186/s12916-026-05124-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Yu-Kun Chen
AU - Wen-Wei Wu
AU - Fan Chen
AU - Lan-Jie Chen
AU - Hao-Xiang Wu
AU - Ying-Nan Wang
AU - Ying Jin
AU - Yu-Tong Chen
AU - Zi-Xian Wang
PY - 2026
DA - 2026/08/08
JO - BMC Medicine
DO - 10.1186/s12916-026-05124-z
UR - https://doi.org/10.1186/s12916-026-05124-z
AB - 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.
SN - 1741-7015
ER -