Multicenter French harmonization study for PD-L1 IHC testing in non-small cell lung cancer

Abstract

Background

Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT).

Methods

IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms. For each matching platform, 22C3, 28-8 and SP263 assays were performed. For non-matching platforms and other antibodies, LDT were developed in each center. A total of 35 stainings were performed for each case across different platforms and antibodies. PD-L1 staining was assessed in tumor cells and immune cells by seven trained thoracic pathologists. For statistical analysis, 1%, 50% and 1%, 5%, 10% expression thresholds were used for tumor cells and immune cells, respectively.

Results

28-8, 22C3 and SP263 assays were highly concordant for tumor cells staining across the 5 Dako or Ventana platforms. Among 27 LDT developed in 7 centers on Dako, Ventana and Leica platforms, 14 (51.8%) demonstrated similar concordance as compared to reference assays for tumor cell staining. Clone SP263 achieved the highest concordance rate across all platforms.Lower concordance was observed for immune cells staining when using a 4-categories scale.

Conclusion

28-8, 22C3 and SP263 assays had close analytical performance for tumor cell staining across 7 centers. Some LDT on Dako, Ventana and Leica platform achieved similar concordance, but caution is warranted for their validation. These LDT will be further validated in order to provide recommendations for the use of assays and LDT for PD-L1 testing in NSCLC.