Development of a Companion Diagnostic for Pembrolizumab in Non-Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1.
* Context.--Programmed death ligand-1 (PD-L1) expression by tumors may enable them to avoid immunosurveillance. Objective.--To develop a PD-L1 immunohistochemical assay using the 22C3 anti-PD-L1 murine monoclonal antibody on the Dako platform as a possible companion diagnostic for pembrolizumab in p...
| Publicado en: | Archives of Pathology & Laboratory Medicine Vol. 140; no. 11; pp. 1243 - 1250 |
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| Autores principales: | , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
College of American Pathologists
Nov2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=119227540&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 119227540 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00039985 1FS jtl: Archives of Pathology & Laboratory Medicine issn: 00039985 maglogo: N pubinfo: dt: Nov2016 vid: 140 iid: 11 pid: 2550 pub: College of American Pathologists place: Northfield, Illinois artinfo: ui: 119227540 119227540 119227540 10.5858/arpa.2015-0542-OA 119227540 ppf: 1243 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Development of a Companion Diagnostic for Pembrolizumab in Non-Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1. aug: au: Dolled-Filhart, Marisa Roach, Charlotte Toland, Grant Stanforth, Dave Jansson, Malinka Lubiniecki, Gregory M. Ponto, Gary Emancipator, Kenneth affil: Department of Molecular Biomarkers and Diagnostics, Merck & Co, Inc, Kenilworth, New Jersey sug: subj: Carcinoma, Non-Small-Cell Lung Drug Therapy Antibodies, Monoclonal Therapeutic Use Carcinoma, Non-Small-Cell Lung Immunology Immunohistochemistry Methods Receptors, Immunologic Drug Effects Patient Selection Methods Clinical Assessment Tools False Negative Results False Positive Results Carcinoma, Non-Small-Cell Lung Mortality Decision Making, Clinical In Vivo Studies Prospective Studies Predictive Value of Tests Evaluation Research ROC Curve Kaplan-Meier Estimator Human ab: * Context.--Programmed death ligand-1 (PD-L1) expression by tumors may enable them to avoid immunosurveillance. Objective.--To develop a PD-L1 immunohistochemical assay using the 22C3 anti-PD-L1 murine monoclonal antibody on the Dako platform as a possible companion diagnostic for pembrolizumab in patients with non-small cell lung cancer. Design.--Tumor samples from 146 patients with non-small cell lung cancer treated with pembrolizumab in KEYNOTE-001 and for whom response data were available were scored according to their staining intensity by a single pathologist using 4 methods: percentage of tumor cells staining at any intensity (PS1), moderate/strong intensity (PS2), strong intensity (PS3), and H-score (PS1 + PS2 + PS3). The cutoff score for predicting response to pembrolizumab was determined using receiver operating characteristic analysis. Progression-free and overall survival were assessed in patients with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (n = 146). Results.--The 4 scoring methods assessed performed similarly; PS1 with a 50% cutoff score is the simplest and easiest method to implement in practice. Response to pembrolizumab was observed in 19 of 44 patients (43%) with a PS1 score of 50% or higher and 8 of 102 patients (8%) with PS1 lower than 50% (odds ratio, 8.93). Median progression-free and overall survival was 4.0 months and not yet reached, respectively, for patients with a PS1 of 50% or higher, and 2.1 and 6.1 months, respectively, for those with PS1 lower than 50%. Conclusion.--The PD-L1 immunohistochemical assay shows the potential for enrichment of trial populations and as a companion diagnostic tool in non-small cell lung cancer. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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