Journal Article

Concordance among four commercially available, validated programmed cell death ligand-1 assays in urothelial carcinoma

Ratcliffe, Marianne, Al-Masri, Hytham, Rebelatto, Marlon C., Scott, Marietta, Scorer, Paul, Walker, Jill, Zajac, Magdalena, Barker, Craig

2019

Overview

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 IC ICArea  ≥ 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Algorithms / Antibodies / Apoptosis / Assay / Assaying / B7-H1 Antigen - analysis / Biomarkers, Tumor - analysis / Biopsy / Bladder cancer / Carcinoma / Carcinoma, Transitional Cell - classification / Cell death / Classification / Correlation analysis / Diagnosis / Diagnostic immunohistochemistry / Diagnostic reagents / Female / Humans / Immune system / Immunohistochemistry / Immunohistochemistry - standards / Ligands / Male / Mathematical analysis / Medicine / Medicine & Public Health / Methods / Middle Aged / Pathology / PD-1 protein / PD-L1 / PD-L1 protein / Reproducibility of Results / Staining / Tumors / Urinary Bladder Neoplasms - classification / Urothelial carcinoma / VENTANA PD-L1 SP263