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

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.

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“…However, there exists considerable interobserver variability in PD-L1 scoring [4][5][6], a factor that can limit the predictive value of PD-L1 testing. There is also no gold standard for "true" PD-L1 scores, though technical concordance of results across multiple pathologists has supported the interchangeability of different PD-L1 assays [3,7].…”

Case Report: Therapeutic Response to Chemo-Immunotherapy in an Advanced Large Cell Lung Carcinoma Patient With Low Values of Multiple Predictive Biomarkers

“…Although PD-L1 expression may help clinicians to choose single-agent immunotherapy for high PD-L1 NSCLC (TPS >50%) or chemo-immunotherapy for positive PD-L1 NSCLC (TPS 1-49%), the variability in immunohistochemical staining antibodies and its heterogeneous expression may result in broad inconsistency of this biomarker (14)(15)(16). Thus, in clinical practice, some other predictive biomarkers emerged for immunotherapy.…”

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“…Because subsequent randomized trials first established PD‐L1 biomarker cutoffs with the 22C3 antibody, it has been the most frequently used predictive antibody and is approved for this use. However, subsequent comparative analyses demonstrated that there was good concordance between the 22C3 and SP263 assays and that both correlated with response to checkpoint inhibitors [206]. Objective responses are concentrated in, but not exclusive to, patients with high TPS, and not all patients with high TPS experience a response to immunotherapy.…”