7. PD-L1 in Triple Negative Breast Cancer – Optimal Testing for Therapeutic Efficacy

Background: The recent IMpassion130 phase 3 trial reported that anti-Programmed death ligand 1 (PD-L1) monoclonal antibody therapy significantly improved progression free survival in triple negative breast cancer (TNBC). The SP142 clone of PD-L1 antibody was used as a predictive assay, which was an outlier antibody in previous harmonisation studies in lung cancer and melanoma. Aims: We aimed to study PD-L1 expression in TNBC by comparing different clones of PD-L1 antibodies. Methods: State-of-the-art quantitative multiplex immunofluorescent (QmIF) staining was performed on three in vitro diagnostic PD-L1 antibody clones (22C3, SP142 and SP263) on 269 TNBCs. To detect tumour and immune cells, cytokeratin and CD45 staining was applied. PD-L1 expression of tumour and immune cells was correlated with PD-L1 RNA expression, clinicopathological parameters, disease-free survival (DFS) and overall survival (OS). Results and conclusions: PD-L1 positivity was described using Combined Positive Score (CPS). We observed a weak correlation between SP142 and SP263 clones (R = 0.265), while the SP142 and 22C3 clones demonstrated a weak inverse correlation (R = –0.256). There was no significant association with clinical outcomes using CPS. Only high 22C3 clone Tumour Proportion Score (TPS) showed significant association with improved DFS, but not OS in multivariate analysis. However, tumours with positively stained SP142 immune cells displayed both enhanced DFS and OS. Correlations between protein and mRNA of PD-L1 are pending. In this study, suboptimal correlation of PD-L1 positivity across different assays was observed. To develop a PD-L1 complementary diagnostic test in TNBC, more analysis and assay harmonisation will be essential. Clinicians and pathologists require this valuable information to predict patient response to anti-PD-L1 therapy, which will represent a tremendous advancement in the management of therapeutically challenging TNBCs. In the cancer immunotherapy era, QmIF ability to simultaneously detect and quantify multiple PD-L1 clones, and also allow accurate evaluation of tumour and immune components objectively, represents a promising tool.