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Meta-Analysis
. 2024 May 16;73(7):132.
doi: 10.1007/s00262-024-03726-1.

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis

Ji-Bin Li #  1 , Ming-Yu Lai #  2 , Zhuo-Chen Lin #  3 , Wen-Long Guan  2 , Yu-Ting Sun  2 , Jing Yang  2 , Wen-Xuan Wang  1   4 , Zhi-Rong Yang  5 , Miao-Zhen Qiu  6
Affiliations
Meta-Analysis

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis

Ji-Bin Li et al. Cancer Immunol Immunother. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value.

Methods: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed.

Results: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values.

Conclusions: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Keywords: Combined positive score; Cutoff value; Gastric cancer; Immune checkpoint inhibitors; Meta-analysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Forest plot for overall survival comparing ICIs plus chemotherapy with chemotherapy alone in global and Asian patients.Predictive value =HR in Asian - HR in globalHR in global×100%
Fig. 2
Fig. 2
Forest plot for the overall survival of ICIs plus chemotherapy versus chemotherapy alone stratified by CPS thresholds. A Global patients and B Asian patients. *HRs and 95%CIs were derived from the reconstruction IPD data.Predictive value =HR in low PD - L1 group - HR in high PD - L1 groupHR in high PD - L1 group×100%
Fig. 3
Fig. 3
The efficacy of ICIs plus chemotherapy on OS and PFS according to CPS thresholds
Fig. 4
Fig. 4
Forest plot for progression-free survival comparing ICIs plus chemotherapy with chemotherapy alone in global and Asian patients. Predictive value =HR in Asian - HR in globalHR in global×100%
Fig. 5
Fig. 5
Forest plot for progression-free survival of ICIs plus chemotherapy versus chemotherapy alone stratified by CPS thresholds. A Global patients and B Asian patients. *HR and 95%CI derived from the reconstruction. Predictive value =HR in low PD - L1 group - HR in high PD - L1 groupHR in high PD - L1 group×100%
See this image and copyright information in PMC

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