Clinical benefit of PD-1 antibody plus chemotherapy in advanced HER2 negative gastric or gastro-oesophageal junction adenocarcinoma according to PD-L1 levels: Post-hoc analysis of RATIONALE-305 and pooled analysis of individual patient-level data
In brief
PD-1 antibody plus chemo reduces death risk ~16% in PD-L1 positive gastric cancer
A pooled analysis of five phase III trials showed that adding a PD-1 inhibitor to first-line chemotherapy lowered overall mortality by about 16% in patients with HER2-negative advanced gastric or gastro-oesophageal junction adenocarcinoma whose tumors had a PD-L1 combined positive score of 1 or higher. Benefit was seen across intermediate PD-L1 levels, but not in tumors with CPS < 1, highlighting the need for PD-L1 testing to guide therapy.
- Journal
- Journal of hematology & oncology (Q1)
- Published
- 20 July 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Ming-Yu Lai, Hao-Xiang Wu, Ming-Ming He, Wen-Long Guan, Sheng Xu, Han Hu, et al.
- PMID
- 42477829
- DOI
- 10.1186/s13045-026-01830-6
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 26 July 2026).
- Picked for Hematology (top studies of the week, 26 July 2026): Recent Hematology research from a high-quartile journal.
- Picked for Pharmacology (medical) (top studies of the week, 26 July 2026).
Abstract
While multiple phase III trials have established the survival benefit of adding a programmed cell death protein 1 (PD-1) antibody to first-line chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, evidence across different programmed cell death ligand 1 (PD-L1) expression levels remains limited, preventing definitive conclusions about the superiority of combination therapy in certain subgroups. We firstly performed a post-hoc analysis of the RATIONALE-305 trial, finding only marginal benefit in the 1 ≤ tumor area positivity (TAP) < 5 and 1 ≤ combined positive score (CPS) < 5 subgroups. Subsequently, we performed a pooled analysis of individual patient-level data from RATIONALE-305 and four additional phase III trials (CheckMate 649, KEYNOTE-062, KEYNOTE-859, and ORIENT-16). The pooled analysis demonstrated that adding a PD-1 antibody to chemotherapy significantly improved overall survival in patients with intermediate PD-L1 levels (1 ≤ CPS < 10: HR, 0.84; 95% CI, 0.75-0.93), including the lower intermediate subset (1 ≤ CPS < 5: HR, 0.85; 95% CI, 0.75-0.97), but not in the CPS < 1 subgroup (HR, 0.96; 95% CI, 0.82-1.14). Progression-free survival results were consistent with those for overall survival, and improvements in objective response rate were observed across all subgroups. In conclusion, this study provides novel evidence that the combination therapy is superior to chemotherapy alone in patients with advanced HER2-negative G/GEJ adenocarcinoma and PD-L1 CPS ≥ 1.
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.