Comparison of PD-L1 Assays in Non-small Cell Lung Cancer: 22C3 pharmDx and SP263.

While the PD-L1 22C3 pharmDx assay is an FDA-approved diagnostic assay for pembrolizumab use, not every pathology laboratory has the Dako Autostainer to use this assay. Since Ventana BenchMark platforms are more common, the Ventana SP263 assay can be used to inform treatment decisions involving nivolumab and pembrolizumab in non-small cell lung cancer (NSCLC). However, some studies have shown discordant results between the two assays. This study aimed was to compare PD-L1 expression using these two assays. A total of 100 samples from consecutive cases of resected NSCLC were tested using the two PD-L1 assays. The agreement rates of the two assays were 88-97% at various cut-offs. There was no significant difference between 22C3 and SP263 in tumour proportion score (p=0.455). The SP263 assay can be used in the place of the 22C3 assay for PD-L1 testing, for guiding therapy with PD-1 axis inhibitors in NSCLC.

Fujimoto D ，Yamashita D ，Fukuoka J ，Kitamura Y ，Hosoya K ，Kawachi H ，Sato Y ，Nagata K ，Nakagawa A ，Tachikawa R ，Date N ，Sakanoue I ，Hamakawa H ，Takahashi Y ，Tomii K ... -  《-》

Multicenter Comparison of 22C3 PharmDx (Agilent) and SP263 (Ventana) Assays to Test PD-L1 Expression for NSCLC Patients to Be Treated with Immune Checkpoint Inhibitors.

Among the several agents targeting the programmed cell death 1 (PD-1) pathway, pembrolizumab is currently the only one approved for the treatment of patients with NSCLC in association with a companion diagnostic assay, the anti-PD-L1 immunohistochemical (IHC) 22C3 PharmDx (Agilent Technologies, Santa Clara, CA) using the Dako Autostainer (Dako, Carpinteria, CA). However, the Dako platform is not present in each pathology department, and this technical limitation is a major problem for the diffusion of the PD-L1 IHC predictive test for pembrolizumab. The Italian Society of Anatomic Pathology and Cytopathology and the Italian Association of Medical Oncology in an independent, multicenter study compared the in vitro diagnostics PD-L1 IHC 22C3 pharmDx test (Agilent) on the Dako Autostainer and the in vitro diagnostics Ventana PD-L1 (SP263) test on the Ventana BenchMark platform (Ventana Medical Systems, Tucson, AZ). Using serial sections from tissue microarrays, 100 lung adenocarcinomas were locally stained and scored in four centers with the same antibody batches. A high analytical correlation (more than 90% at the lower 95% confidence interval [CI] value) between PD-L1 expression levels obtained with the 22C3 and SP263 assays was observed. At the proposed clinically relevant cutoffs (≥50% and ≥1%), the overall concordances between 22C3 and SP263 data were 0.99 (95% CI: 0.96-1) and 0.80 (95% CI: 0.68-0.91), respectively. The lower agreement between data obtained with the 22C3 and SP263 clones at the cutoff of 1% or higher was mainly related to the lower (about 80%) interrater agreement at this cutoff with each clone. These results indicate a high correlation between PD-L1 IHC expression data obtained with the Agilent PD-L1 IHC 22C3 pharmDx and the Ventana PD-L1 (SP263) tests in NSCLC and suggest that the two assays could be utilized interchangeably as an aid to select patients for first-line and second-line treatment with pembrolizumab and potentially with other anti-PD-1/PD-L1 checkpoint inhibitors.

Marchetti A ，Barberis M ，Franco R ，De Luca G ，Pace MV ，Staibano S ，Volante M ，Buttitta F ，Guerini-Rocco E ，Righi L ，D'antuono T ，Scagliotti GV ，Pinto C ，De Rosa G ，Papotti M ... -  《-》

Comparison of PD-L1 immunohistochemistry assays and response to PD-1/L1 inhibitors in advanced non-small-cell lung cancer in clinical practice.

Several studies have demonstrated analytical comparability between different PD-L1 assays, but their clinical validity in non-small-cell lung cancer in terms of response to treatment outside clinical trials has not been established. The aim of our study is to assess the analytical performance of laboratory-developed tests for Ventana SP263 and Agilent/Dako 22C3, and to investigate the association between PD-L1 assays and response to PD-1/L1 inhibitors. PD-L1 SP263 and 22C3 assays were performed on 302 consecutive non-small-cell lung carcinoma samples Both assays were optimised for use on the automated Ventana BenchMark Ultra platform. Scoring algorithms for staining of the tumour cells using the established cut-offs were applied to all samples. Best overall response (BOR) for 44 patients treated with either nivolumab, pembrolizumab or atezolizumab were assessed using recist version 1.1 and correlated with PD-L1 assay results. Assays showed good agreement, with a concordance correlation coefficient of 0.86 [95% confidence interval (CI) = 0.82-0.90)]. Comparing the assays using cut-offs of 1%, 5%, 10%, 1-49% and ≥50% showed an association between the two assays (P < 0.0001). The SP263 10% cut-off (P = 0.032) was associated with BOR, whereas the 1% (P = 0.087) and 5% (P = 0.051) cut-offs were not. In contrast 22C3, cut-offs of 1% (P = 0.019), 5% (P = 0.025) and 10% (P = 0.014) were all associated with BOR. The SP263 and 22C3 LDTs demonstrated good analytical concordance, and correlation with response to PD-1/L1 inhibitors.

Villaruz LC ，Ancevski Hunter K ，Kurland BF ，Abberbock S ，Herbst C ，Dacic S ... -  《-》

Use of the 22C3 anti-PD-L1 antibody to determine PD-L1 expression in multiple automated immunohistochemistry platforms.

Ilie M ，Khambata-Ford S ，Copie-Bergman C ，Huang L ，Juco J ，Hofman V ，Hofman P ... -  《PLoS One》

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

Savic S ，Berezowska S ，Eppenberger-Castori S ，Cathomas G ，Diebold J ，Fleischmann A ，Jochum W ，Komminoth P ，McKee T ，Letovanec I ，Jasarevic Z ，Rössle M ，Singer G ，von Gunten M ，Zettl A ，Zweifel R ，Soltermann A ，Bubendorf L ... -  《-》