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Updated: Jan 20, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Concordance among four commercially available, validated programmed cell death ligand-1 assays in urothelial
Magdalena Zajac1, Marietta Scott2, Marianne Ratcliffe1
1Oncology Companion Diagnostics Unit, Precision Medicine, R&D Oncology, AstraZeneca, Cambridge, UK.
Background:
Antibodies targeting the programmed cell death-1 (PD-1)/PD-ligand 1 (PD-1/PD-L1) checkpoint have shown promising clinical activity in patients with advanced urothelial carcinoma (UC). Expression of PD-L1 in UC tumors has been investigated using different antibody clones, staining protocols, and scoring algorithms. The aim was to establish the extent of concordance among PD-L1 immunohistochemistry (IHC) assays.
Methods:
Tumor biopsy samples (N = 335) were assessed using four commercially available PD-L1 assays: VENTANA SP263, VENTANA SP142, PD-L1 IHC 28-8 pharmDx, and PD-L1 IHC 22C3 pharmDx. PD-L1 analytical staining and classification concordance, including agreement between clinically relevant scoring algorithms, were investigated using overall/positive/negative percentage agreement (OPA/PPA/NPA).
Results:
Good analytical correlation was observed among the VENTANA SP263, PD-L1 IHC 22C3 pharmDx, and PD-L1 IHC 28-8 pharmDx assays for tumor cell (TC) and immune cell (IC) PD-L1 staining with Spearman rank coefficients of 0.92-0.93 for TCs and 0.88-0.91 for ICs. However, concordance (preset criterion: ≥85%) between patient PD-L1 status when applying the TC or ICICArea ≥ 25% (VENTANA SP263) cutoff was only achieved for PD-L1 IHC 22C3 pharmDx versus VENTANA SP263 (OPA 92.2%, PPA 86.4%, NPA 95.4%). Differences were observed between patient populations with UC tumors classified as PD-L1 high versus PD-L1 low/negative using combined positive score (CPS) ≥1, CPS ≥10, IC ≥5%, and TC/IC ≥25%.
Conclusions:
The VENTANA SP263 and PD-L1 IHC 22C3 pharmDx assays are analytically similar in UC. When the different PD-L1 assays were combined with their specified clinical scoring algorithms, differences were seen in patient classification driven by substantial differences in scoring approaches.
Insights
Four PD-L1 assays show analytical similarity in urothelial carcinoma (UC). However, differences in scoring algorithms lead to varied patient classification, impacting treatment decisions for PD-L1 expression in UC.
Area of Science:
- Oncology
- Immunotherapy
- Urothelial Carcinoma Research
Background:
- Programmed cell death-1 (PD-1)/PD-ligand 1 (PD-1/PD-L1) checkpoint inhibitors demonstrate efficacy in advanced urothelial carcinoma (UC).
- Standardization of PD-L1 immunohistochemistry (IHC) assays is crucial due to varying antibody clones, protocols, and scoring methods in UC.
Purpose of the Study:
- To evaluate the concordance among four commercially available PD-L1 IHC assays in urothelial carcinoma.
- To assess the impact of different scoring algorithms on patient classification based on PD-L1 expression.
Main Methods:
- Analysis of 335 tumor biopsy samples from patients with advanced UC.
- Utilized four PD-L1 assays: VENTANA SP263, VENTANA SP142, PD-L1 IHC 28-8 pharmDx, and PD-L1 IHC 22C3 pharmDx.
- Investigated analytical staining concordance and classification agreement using Overall Percentage Agreement (OPA), Positive Percentage Agreement (PPA), and Negative Percentage Agreement (NPA).
Main Results:
- Strong analytical correlation observed between VENTANA SP263, PD-L1 IHC 22C3 pharmDx, and PD-L1 IHC 28-8 pharmDx for tumor cell (TC) and immune cell (IC) PD-L1 staining.
- High concordance (OPA 92.2%, PPA 86.4%, NPA 95.4%) was achieved between PD-L1 IHC 22C3 pharmDx and VENTANA SP263 using specific cutoffs (TC or ICICArea ≥ 25%).
- Significant differences in patient classification were noted when applying various scoring algorithms (e.g., Combined Positive Score [CPS] ≥1, IC ≥5%, TC/IC ≥25%) across the assays.
Conclusions:
- VENTANA SP263 and PD-L1 IHC 22C3 pharmDx assays exhibit analytical similarity in UC.
- Discrepancies in patient classification arise from distinct scoring approaches when combining PD-L1 assays with their specified clinical algorithms.
- Standardization of PD-L1 scoring is essential for consistent patient stratification in UC clinical practice.
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