PD-L1 testing of non-small cell lung cancer using different antibodies and platforms: a Swiss cross-validation study

Abstract

With the approval of pembrolizumab for first-and second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC), PD-L1 testing by immunohistochemistry (IHC) has become a necessity. However, the DAKO autostainer ASL48 for the FDA approved DAKO 22C3 pharmDx assay is not broadly available in Switzerland and other parts of Europe. The primary goal of this study was to cross-validate the 22C3 anti-PD-L1 antibody on Benchmark Ultra (VBMU) and Leica Bond (LBO) immunostainers. IHC protocols were developed for 22C3 on both platforms with the 22C3phDx using ASL48 as reference. A tissue microarray (TMA) was constructed from 23 NSCLC specimens with a range of PD-L1 staining results. Empty TMA sections and the 22C3 antibody were distributed to 16 participants for staining on VBMU (8 centers) and/or LBO (12 centers) using the centrally developed protocols. Additionally the performance of the Ventana SP263 assay was tested in five centers. IHC scoring was performed centrally. Categorical PD-L1 staining (0-49% vs. 50-100%) did not significantly differ between centers using VBMU, whereas data from LBO were highly variable (p < 0.001). The SP263 assay was well concordant with 22C3 on VBMU and with 22C3 pharmDx. PD-L1 IHC using a standardized 22C3 protocol on VBMU provides satisfactory results in most centers. The SP263 assay is confirmed as a valid alternative to 22C3 pharmDx. 22C3 PD-L1 IHC on LBO shows major staining variability between centers, highlighting the need for local validation and adjustment of protocols.

Performance of Ventana SP263 PD‐L1 assay in endobronchial ultrasound guided‐fine‐needle aspiration derived non‐small‐cell lung carcinoma samples

“…Savic et al cross‐validated the 22C3 anti PD‐L1 antibody on benchmark Ultra (VBMU) and Leica Bond immunostainer by centrally developing and validating new PD‐L1 IHC protocols. They noted that the average median TPS of SP263 was highly comparable with the reference 22C3 26 . Lozano et al studied PD‐L1 expression on Papanicolaou‐stained cytological smears and compared with formalin‐fixed paraffin‐embedded samples (cytological cell blocks and surgical resection specimens) in 57 set of samples using 2 IHC 22C3 pharmDx assay and the Ventana SP263 Assay.…”

Role of Pd-L1 Assessment in the Aspect of Molecular-Genetic Classification of Colorectal Cancer. Current State of the Problem

“…Иммуногистохимическая (ИГХ) оценка экспрессии PD-1/PD-L1 применяется при меланоме, уротелиальной карциноме, раке почки, немелкоклеточном раке легкого, раке молочной железы, лимфоме Ходжкина и других злокачественных новообразованиях [35]. Золотым стандартом диагностики является оценка PD-L1-экспрессии при немелкоклеточном раке легкого, а PD/PD-L1блокаторы применяются в качестве терапии первой и второй линий у больных с данной патологией [36].…”

Etiological factors and characterization of patients with lung cancer at the National Cancer Institute, Paraguay

“…En la actualidad el adenocarcinoma de pulmón es el cáncer de pulmón primario más común visto en los Estados Unidos y (36) en la gran parte de los países del mundo tiene una fuerte asociación con el tabaquismo previo . Estos cambios tienen relación con modificaciones en la fabricación del cigarrillo (introducción de filtros y contenido de alquitrán reducido) y a los efectos de fumar, cese y reducción de la prevalencia del (37) tabaquismo . Las tasas de carcinoma escamoso más altas fueron encontradas en Antofagasta, Chile, lo que coincide con la prevalencia de tabaquismo particularmente altas reportadas en este país (14,15,38,39) y en la región específica .…”