scholarly journals Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer

2020 ◽  
Vol Volume 13 ◽  
pp. 667-683 ◽  
Author(s):  
Shiqiang Wang ◽  
Chongling Hu ◽  
Fei Xie ◽  
Yanhui Liu
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Death Receptor ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe?

2016 ◽  
Vol 140 (4) ◽  
pp. 326-331 ◽  
Author(s):  
Keith M. Kerr ◽  
Fred R. Hirsch
Keyword(s):  
Lung Cancer ◽  
Death Receptor ◽  
Cancer Therapeutics ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Area ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Biomarker Testing

The approval of anti-programmed death receptor (PD)-1 therapies for non–small cell lung cancer has directed the spotlight on programmed death ligand-1 (PD-L1) immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti–PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti–PD-1 and anti–PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing.

scholarly journals 38 Clinical validation of an image analysis assay for determining programmed death-ligand 1 (22C3) in non-small cell lung cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A39-A39
Author(s):  
Roberto Gianani ◽  
Will Paces ◽  
Elliott Ergon ◽  
Kristin Shotts ◽  
Vitria Adisetiyo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Image Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Clinical Validation ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

BackgroundDetermination of programmed death-ligand 1 (PD-L1) level in tumor by immunohistochemistry (IHC) is widely used to predict response to check point inhibitor therapy. In particular, the Dako PD-L1 (22C3) antibody is a common companion diagnostic to the monoclonal antibody drug Keytruda® (pembrolizumab) in non-small cell lung cancer (NSCLC).1 However, for the practicing pathologist, interpretation of the PD-L1 (22C3) assay is cumbersome and time consuming. Manual pathologist scoring also suffers from poor intra- and inter-pathologist precision, particularly around the cut-off point.2 In this clinical validation study, we developed an image analysis (IA) based solution to accurately and precisely score digital images obtained from PD-L1 stained NSCLC tissues for making clinical enrollment decisions.Methods10 NSCLC tissue samples were purchased from a qualified vendor and IHC stained for PD-L1; 4 of these samples had serial sections stained on two separate days. Stained slides were scanned at 20X magnification and analyzed using Flagship Biosciences’ IA solutions that quantify PD-L1 expression and separate tumor and stromal compartments. Resulting image markups of cell detection and PD-L1 expression were reviewed by an MD pathologist for acceptance. PD-L1 staining was evaluated by digital IA in the sample’s tumor compartment for Total Proportion Score (TPS,%). Assay specificity was defined by ≥ 90% of the tissue cohort exhibiting appropriate cell recognition (≥ 90% cells correctly recognized as determined by the pathologist), with ≤ 10% false positive rate for staining classification. Sensitivity was defined by ≥ 90% of the cohort exhibiting appropriate cell identification (≥ 90% cells correctly identified), with ≤ 10% false negative rate for staining classification. Accuracy was defined by the combination of sensitivity and specificity and precision was defined by concordance of the binned TPS (<1%, ≥ 1%, ≥ 50%) in ≥ 80% of the samples stained on multiple days.ResultsThe preliminary results show that IA can yield high analytical sensitivity, specificity, accuracy, and precision in the determination of the PD-L1 score. 100% of the tissue cohort met criteria for analytical specificity, sensitivity, and accuracy and 100% of the samples stained on multiple days met the precision criteria.ConclusionsThis data demonstrates the feasibility of an IA approach as applied to PD-L1 (22C3) scoring. Ongoing experiments include application of the developed 22C3 algorithm on a separate cohort of 20 NSCLC samples to determine the correlation of digital scoring and scoring obtained by three pathologists. Additionally, we will evaluate the precision obtained by digital scoring in relation to the intra- and inter-pathologist concordance.ReferencesIncorvaia L, Fanale D, Badalamenti G, et al. Programmed death ligand 1 (PD-L1) as a predictive biomarker for pembrolizumab therapy in patients with advanced non-small-cell lung cancer (NSCLC). Adv Ther 2019;36:2600–2617.Rimm DL, Han G, Taube JM, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non–small cell lung cancer. JAMA Oncol 2017;3:1051–1058.

Influenza vaccination in patients with lung cancer receiving anti–programmed death receptor 1 immunotherapy does not induce immune-related adverse events

2018 ◽  
Vol 104 ◽  
pp. 182-187 ◽  
Author(s):  
Dirk H. Wijn ◽  
Geert H. Groeneveld ◽  
Albert M. Vollaard ◽  
Mirte Muller ◽  
Jacco Wallinga ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Influenza Vaccination ◽  
Death Receptor ◽  
Programmed Death
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