PD-L1/PD-1 checkpoint inhibitors have shown clinical activity in UBC. It has been shown that PD-L1 expression on TC and/or IC correlates with clinical efficacy. In this study (ML39708) we examined technical comparability and inter-reader agreement of 4 clinically relevant assays for PD-L1 expression on IC and TC in locally advanced UBC.
Archived formalin-fixed paraffin-embedded sections from 30 patients with locally advanced UBC (70% cystectomies, 30% transurothelial resections) were selected from 150 cases based on PD-L1 status per VENTANA SP142 IC 5% (10 cases each). The study cohort was stained for PD-L1 using SP142, SP263 (VENTANA), 22C3, and 28-8 (DAKO) assays at two sites according to manufacturer protocols. Stainings were blinded and scored at 5 sites for the PD-L1 expression on IC (% per tumor area) and TC (%). All readers were trained on scoring IC with SP142.
Percentage of IC cells staining for PD-L1 varied from 6.54 to 8.18%, and TC from 5.46 to 15.85%, depending on the assay used (Table). For each assay, IC staining varied slightly to moderately between readers, with small non-significant differences between assays. Results for TC were comparable except for significantly lower staining with SP142. Pairwise comparison revealed –0.3 to 1.6% differences in adjusted means between assays for IC, and for TC, –10.5 to –7.8% (SP142 vs other assays) and –1.9 to 2.7% (other comparisons). Retrospective allocation to binary cut-offs (1%, 5% and 10%) for IC or TC only predominantly showed substantial or high Kappa agreement scores (0.6–0.8) for IC and TC between assays for each reader.Table:
|Assay||PD-L1 on IC %||Reader ICC†||PD-L1 on TC %||Reader ICC†|
|(95% CI)*||(95% CI)*|
|VENTANA SP142||8.18 (7.32–9.03)||0.699||5.46 (2.85–8.07)||0.609|
|VENTANA SP263||7.08 (6.22–7.94)||0.729||15.85 (13.24–18.47)||0.805|
|DAKO 22C3||6.54 (5.68–7.39)||0.532||13.19 (10.57–15.80)||0.883|
|DAKO 28-8||6.88 (6.02–7.74)||0.573||15.15 (12.54–17.77)||0.845|
Adjusted means for each assay;†
Intra-class correlation per test between 5 readers
This is the first multicenter study for analytical comparison of PD-L1 IHC staining on IC and TC in UBC. High concordance rates across all assays were achieved between trained readers for scoring PD-L1 on IC and TC.
Clinical trial identification
Legal entity responsible for the study
Roche Pharma AG
Roche Pharma AG
A. Hartmann: Membership of an advisory board: Roche, MSD, AstraZeneca Corporate-sponsored research: Novartis, Biontech, Illumina, Nanostring, Quiagen. G. Baretton: Membership of an advisory board Roche, Bristol-Myers Squibb, AstraZeneca Corporate-sponsored research Roche, Bristol-Myers Squibb. F. Lasitschka: Membership of an advisory board: Roche NSCLC regional advisory board. Bristol-Myers Squibb NSCLC regional advisory board Corporate-sponsored research: Roche PLACU study. P. Schirmacher: Roche (Research, Honorarium) Bristol-Myers Squibb (Research, Honorarium), MSD (Research, Honorarium), AstraZeneca (Research, Honorarium), Novartis (Research, Honorarium). T. Braunschweig: Membership of an advisory board and invited guest speaker: Bristol-Myers Squibb Invited guest speaker: MSD Corporate-sponsored research: Roche. R. Tauber: Membership of an advisory board: Roche, Sanofi, Bristol-Myers Squibb) Corporate-sponsored Research: conduct as subinvestigator of clinical trials. S. Hieke-Schulz: Employee Roche Pharma AG. J. Ammann: Stock ownership: Roche Pharmaceuticals Other substantive relationships: Employee of Roche Pharma AG. W. Weichert: Conflicts of interest Advisory boards for Roche, AstraZeneca, MSD, Bristol-Myers Squibb, Pfizer, Novartis, Boehringer. Collaborative research with Roche, Novartis, AstraZeneca, Boehringer. All other authors have declared no conflicts of interest.