Comparability of PD-L1 immunohistochemistry assays for non-small-cell lung cancer: a systematic review.

Bregje M Koomen,Michel M Van Den Heuvel,Stefan M Willems,Sushil K Badrising

doi:10.1111/his.14040

Abstract

Programmed cell death ligand 1 (PD‐L1) immunohistochemistry is used to determine which patients with advanced non‐small‐cell lung cancer (NSCLC) respond best to treatment with PD‐L1 inhibitors. For each inhibitor, a unique immunohistochemical assay was developed. This systematic review gives an up‐to‐date insight into the comparability of standardised immunohistochemical assays and laboratory‐developed tests (LDTs), focusing specifically on tumour cell (TC) staining and scoring. A systematic search was performed identifying publications that assessed interassay, interobserver and/or interlaboratory concordance of PD‐L1 assays and LDTs in tissue of NSCLC patients. Of 4294 publications identified through the systematic search, 27 fulfilled the inclusion criteria and were of sufficient methodological quality. Studies assessing interassay concordance found high agreement between assays 22C3, 28‐8 and SP263 and properly validated LDTs, and lower concordance for comparisons involving SP142. A decrease in concordance, however, is seen with use of cut‐offs, which hampers interchangeability of PD‐L1 immunohistochemistry assays and LDTs. Studies assessing interobserver concordance found high agreement for all assays and LDTs, but lower agreement with use of a 1% cut‐off. This may be problematic in clinical practice, as discordance between pathologists at this cut‐off may result in some patients being denied valuable treatment options. Finally, five studies assessed interlaboratory concordance and found moderate to high agreement levels for various assays and LDTs. However, to assess the actual existence of interlaboratory variation in PD‐L1 testing and PD‐L1 positivity in clinical practice, studies using real‐world clinical pathology data are needed.

Highlights

Since the approval of the first immune check-point inhibitor in 2011,1-3 immunotherapy has become an important part of treatment for several forms ofFor each immune check-point inhibitor, a separate immunohistochemistry (IHC) Programmed cell death ligand 1 (PD-L1) assay has been developed
The PD-L1 IHC SP263 assay was developed for durvalumab, but it has received Conformite Europeenne (CE) marking for identification of patients eligible for treatment with pembrolizumab and of patients most likely to benefit from treatment with nivolumab.[19,20]
This review focuses on concordance of tumour cell (TC) staining and scoring, as treatment decisions for non-small-cell lung cancer (NSCLC) patients are based on scoring of PD-L1 expression on TCs in clinical practice

Summary

Introduction

Since the approval of the first immune check-point inhibitor in 2011,1-3 immunotherapy has become an important part of treatment for several forms ofFor each immune check-point inhibitor, a separate immunohistochemistry (IHC) PD-L1 assay has been developed. The PD-L1 IHC SP263 assay was developed for durvalumab, but it has received CE marking for identification of patients eligible for treatment with pembrolizumab and of patients most likely to benefit from treatment with nivolumab.[19,20]. Using all these different assays to test for PD-L1 expression in one pathology laboratory is not feasible. A multitude of studies examining these issues has been published, such as the Blueprint PD-L1 IHC Assay Comparison Project[22] or the harmonisation studies by Ratcliffe et al.,[23] Rimm et al.[24] and Scheel et al.[25] Others, such as Bu€ttner et al.,[19] have reviewed the analytical performance of PD-L1 IHC assays previously. The aim of this study was to systematically review all studies that assessed interassay, interobserver and/or interlaboratory concordance of PD-L1 IHC assays and LDTs, and in so doing provide an updated insight into the comparability of these standardised assays and LDTs

Objectives

Methods

Results

Conclusion