Discordant PD-L1 results between 28-8 and 22C3 assays are associated with outcomes of gastric cancer patients treated...

Area of Science:

• Oncology
• Immunotherapy
• Biomarker Research

Background:

• Evaluating programmed death-ligand 1 (PD-L1) expression is crucial for predicting response to immune checkpoint inhibitors.
• Nivolumab plus chemotherapy is a standard first-line treatment for advanced gastric cancer.
• The concordance of different PD-L1 assays and its clinical implications require further investigation.

Purpose of the Study:

• To assess the concordance between the 28-8 and 22C3 PD-L1 assays in advanced gastric cancer patients.
• To determine the impact of PD-L1 assay discordance on efficacy outcomes in patients treated with nivolumab plus chemotherapy.

Main Methods:

• Retrospective analysis of 143 advanced gastric cancer patients treated with first-line nivolumab plus chemotherapy.
• Comparison of PD-L1 staining results using the 28-8 and 22C3 assays, evaluating combined positive score (CPS) positivity.
• Analysis of inter-observer variability and correlation with progression-free survival (PFS).

Main Results:

• The 28-8 and 22C3 assays demonstrated suboptimal concordance, with agreement rates ranging from 78.3% to 88.8% across different CPS cutoffs.
• Inter-observer variability was low for both assays (intra-class correlation coefficient 0.89 and 0.88).
• Discordant PD-L1 results were associated with shorter progression-free survival (PFS) compared to concordantly positive results (P=0.013).

Conclusions:

• PD-L1 assays using 28-8 and 22C3 antibodies exhibit suboptimal concordance in advanced gastric cancer.
• Inter-observer variability is not a significant factor influencing PD-L1 assessment.
• Discordance between PD-L1 assays may negatively affect treatment efficacy outcomes for patients receiving nivolumab plus chemotherapy.