PD-L1 expression in gastric cancer: interchangeability of 22C3 and 28-8 pharmDx assays for responses to immunotherapy

• Published in: Modern pathology Vol. 34; no. 9; pp. 1719 - 1727
• Main Authors: Ahn, Soomin, Kim, Kyoung-Mee
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.09.2021; Nature Publishing Group US; Elsevier Limited
• Subjects: 631/67/1504; 692/53/2423; 82/51; Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Apoptosis; B7-H1 Antigen - analysis; B7-H1 Antigen - drug effects; Biomarkers, Tumor - analysis; Clinical trials; Female; Gastric cancer; Humans; Immunohistochemistry - methods; Immunotherapy; Laboratory Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Nivolumab - therapeutic use; Paraffin; Pathology; Patients; PD-L1 protein; Pembrolizumab; Reproducibility of Results; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Tumor cells
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-021-00823-9

Recent clinical trials have shown the promising therapeutic effects of pembrolizumab and nivolumab in patients with advanced gastric cancer. Currently, the programmed death ligand-1 (PD-L1) 22C3 pharmDx assay is the only companion diagnostic assay for assessing the safety and effectiveness of pembrolizumab. The purpose of this study was to compare 22C3 pharmDx and 28-8 pharmDx, a complementary diagnostic assay for nivolumab, in gastric cancer. In this study, 22C3 and 28-8 pharmDx assays were performed on the same formalin-fixed, paraffin-embedded tissue blocks of gastric adenocarcinoma clinical samples (n = 55). The concordance rate was evaluated using combined positive score (CPS) cutoffs of 1, 10, and 50. PD-L1 positivity with CPS ≥ 1 was 45.5% using the 22C3 pharmDx assay and 49.1% using the 28-8 pharmDx assay. At a CPS cutoff of 1, the overall percentage agreement was 96.4%. The positive and negative percentage agreements were 93.3% and 100%, respectively. All cases positive for PD-L1 using the 22C3 pharmDx assay were also positive using the 28-8 pharmDx assay. At a CPS cutoff of 10, the overall percentage agreement was 96.4%. At a CPS cutoff of 50, the two assays exhibited 100% concordance. Nonspecific cytoplasmic staining in the background tissues and tumor cells was often observed in the 28-8 pharmDx assay. When the results of the two assays were matched for response to immunotherapy, the overall response rate was higher in patients with a PD-L1 CPS ≥ 1 than in PD-L1-negative patients (22C3 pharmDx, P = 0.001; 28-8 pharmDx, P = 0.002). In conclusion, PD-L1 22C3 and 28-8 pharmDx assays were highly comparable at CPS cutoffs of 1, 10, and 50 in gastric cancer. These results provide evidence for the potential interchangeability of the two PD-L1 assays in gastric cancer.