PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs

Abstract

Purpose We provide a comparison between 22C3 pharmDx and SP263 assay, for evaluating programmed death ligand 1 (PD-L1) expression in advanced gastric cancer (GC) patients.Materials and Methods The PD-L1 immunohistochemistry by 22C3 pharmDx and SP263 assays was performed in the center of the tumor (CT) and invasive margin (IM) in 379 GC tissues using tissue microarrays and interpreted as combined positive score (CPS) and tumor proportion score (TPS). Of the total samples, 55 samples were independently reviewed by five pathologists.Results The two assays showed a high correlation in both the CPS and TPS. At a CPS ≥ 1 cut-off, 219 (57.8%) and 231 (60.9%) GCs were positive for PD-L1 with the 22C3 and SP263 assays, and at ≥ 10 cut-off, 37 (9.8%) and 36 (9.5%) GCs were positive, respectively. The overall percent agreement (OPA) was greater than 90% with CPS ≥ 1 and ≥ 10 cut-offs, and TPS ≥ 1% and ≥ 10% cut-offs. There was higher OPA between the two assays with a CPS cut-off ≥ 10 (99.2%) than ≥ 1 (94.7%). The percent agreement between the CT and IM was higher with a CPS cut-off ≥ 10 (92.9%) than ≥ 1 (77.6%). Patient with positive expression at CPS ≥ 5 cut-off had a significantly better outcomes in both assays. Interobserver variability among five pathologists was higher than the assay variability.Conclusion Two assays for PD-L1 expression in GC showed high agreement. These results provide guidance for selecting eligible patients with GC for pembrolizumab treatment.

Programmed cell death protein 1/programmed death ligand 1 but not HER2 is a potential therapeutic target in gastric neuroendocrine carcinoma

“…Regarding the scoring algorithms based on PD‐L1 immunohistochemistry, the PD‐L1 CPS rather than the tumour proportion score (i.e. the percentage of positive tumour cells alone) is considered to be a robust and reliable method for predicting the response to pembrolizumab in patients with gastric cancer 17,26 . Kulangara et al .…”

“…However, studies have demonstrated that both the 22C3 antibody and the SP263 antibody are highly concordant in PD‐L1 scoring, suggesting that the two assays may be interchangeable 30–32 . In fact, a recent study performed PD‐L1 immunohistochemistry with both the 22C3 antibody and the SP263 antibody in 379 gastric cancer cases, and showed excellent agreement of the PD‐L1 CPS between the two antibodies; with a CPS cut‐off of 1, 219 (57.8%) and 231 (60.9%) cases were positive for PD‐L1 according to the 22C3 antibody and the SP263 antibody, respectively 26 . Therefore, the results would be most likely to be in agreement with the present results if the 22C3 antibody had been used in the present study.…”

“…the percentage of positive tumour cells alone) is considered to be a robust and reliable method for predicting the response to pembrolizumab in patients with gastric cancer. 17,26 Kulangara et al compared the PD-L1 CPS and the tumour proportion score as biomarkers to evaluate their ability to predict the response to pembrolizumab in the KEYNOTE-059 study, a phase 2 trial evaluating pembrolizumab alone or in combination with chemotherapy in patients with recurrent or metastatic gastric or gastro-oesophageal cancer. 17 The study found that the objective response to pembrolizumab was significantly associated with the PD-L1 CPS but not with the tumour proportion score.…”

Prediction of <i>TP53</i> mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer

“…The EBV status was tested using EBV in-situ hybridization as previously described [ 20 ]. A fluorescein-conjugated EBV encoded small RNA (EBER) oligonucleotide probe (INFORM EBVencoded RNA probe, Ventana Medical Systems) was used, and positive cases were defined as diffuse nuclear reactivity for EBER in tumor cells.…”

Targeting Oncoimmune Drivers of Cancer Metastasis

“…Biomarkers that predict potential responders to anti-PD1/PDL1 therapy have been strenuously investigated by analyzing patient-derived specimens using advanced technology, and several biomarkers, including PDL1 expression, microsatellite instability (MSI), and mutation burden (the number of non-synonymous single nucleotide variants) in tumor cells have been identified [ 168 , 169 ]. However, these are not necessarily correlated with clinical outcomes, and more precise and accurate biomarkers are still being explored in clinical settings.…”