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IBCN 2018: PD-L1 Expression According to Five Monoclonal Antibodies in Urothelial Cell Cancer

Rotterdam, The Netherlands (UroToday.com) High PD-L1 expression is frequently applied as an inclusion criterion or stratification factor in clinical trials on immune checkpoint inhibitors (ICIs). However, conflicting results have been published regarding the predictive and prognostic value of PD-L1 expression in urothelial cancer (UC), which may be confounded by the use of different PD-L1 companion diagnostics. The objective of this study was to compare PD-L1 expression of five commercially available PD-L1 antibodies in muscle-invasive UC.

Tissue Microarrays (TMA) containing samples of 139 muscle-invasive UC patients were stained with the anti-PD-L1 antibodies: 22C3, 28-8, SP142, SP263, and E1L3N on the Ventana Benchmark (SP142, SP263) and DAKO platforms (22C3, 28-8, E1L3N). PD-L1 expression was manually scored on tumor cells (TC) and infiltrating immune cells (IC). Next, the PD-L1 status was determined according to corresponding assay specifications used in clinical trials.

PD-L1 expression was higher on TC than IC using antibodies 22C3, 28-8, SP263 and E1L3N, while SP142 demonstrated less PD-L1 expression on TC. PD-L1 status was positive in 20% to 27% of patients. The percentage agreement in PD-L1 status between individual antibody clones: i) varied from 60% to 90%, ii) was lowest for E1L3N and SP142, and iii) was better when based on a higher cutoff value for 22C3 (³10%) and 28-8 (³5%). Fleiss’ Kappa as an index of inter-assay agreement was 0.506 for all antibodies (PD-L1 status identical in 64%), it improved to 0.617 considering 22C3, 28-8, SP-142 and SP263 (PD-L1 status identical in 78%), and was best considering only 22C3, 28-8 and SP263 (Fleiss’ Kappa 0.674, PD-L1 status identical in 84%).

In summary, they found a substantial concordance in PD-L1 status between the most frequently used PD-L1 companion diagnostics. In the majority of cases, the PD-L1 status was similar by each companion diagnostic antibody, indicating that the application of different companion PDL1 antibodies may have limited implications on therapeutic decision making in ICI treatment for UC patients.

Presented by: Maud Rijnders, Erasmus MC-Cancer Institute, Rotterdam, The Netherland

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands