Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy

Background Immune checkpoint inhibitors (ICI) are now standard-of-care treatment for patients with metastatic gastric cancer (GC). To guide patient selection for ICI therapy, programmed death ligand-1 (PD-L1) biomarker expression is routinely assessed via immunohistochemistry (IHC). However, with an increasing number of approved ICIs, each paired with a different PD-L1 antibody IHC assay used in their respective landmark trials, there is an unmet clinical and logistical need for harmonization. We investigated the interchangeability between the Dako 22C3, Dako 28-8 and Ventana SP-142 assays in GC PD-L1 IHC. Methods In this cross-sectional study, we scored 362 GC samples for PD-L1 combined positive score (CPS), tumor proportion score (TPS) and immune cells (IC) using a multiplex immunohistochemistry/immunofluorescence technique. Samples were obtained via biopsy or resection of gastric cancer. Results The percentage of PD-L1-positive samples at clinically relevant CPS >= 1, >= 5 and >= 10 cut-offs for the 28-8 assay were approximately two-fold higher than that of the 22C3 (CPS >= 1: 70.3 vs 49.4%, p < 0.001; CPS >= 5: 29.1 vs 13.4%, p < 0.001; CPS >= 10: 13.7 vs 7.0%, p = 0.004). The mean CPS score on 28-8 assay was nearly double that of the 22C3 (6.39 +/- 14.5 vs 3.46 +/- 8.98, p < 0.001). At the clinically important CPS >= 5 cut-off, there was only moderate concordance between the 22C3 and 28-8 assays. Conclusion Our findings suggest that scoring PD-L1 CPS with the 28-8 assay may result in higher PD-L1 scores and higher proportion of PD-L1 positivity compared to 22C3 and other assays. Until stronger evidence of inter-assay concordance is found, we urge caution in treating the assays as equivalent.

Automated summary

Our study showed that PD-L1 CPS scores and positivity rates are higher with the 28-8 assay compared to the 22C3 and other assays in GC PD-L1 IHC. Therefore, caution should be exercised in considering these assays as equivalent until stronger evidence of inter-assay concordance is established.