title: Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non-Small Cell Lung Cancer.
abstract: Purpose:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized, and different assay methods could lead to inappropriate treatment selection. This study establishes the extent of concordance between three validated, commercially available PD-L1 IHC diagnostic assays for NSCLC patients [Ventana SP263 (durvalumab), Dako 22C3 (pembrolizumab), and Dako 28-8 (nivolumab)].Experimental Design:Five hundred formalin-fixed, paraffin-embedded archival NSCLC samples were obtained from commercial sources. Stained slides were read in batches on an assay-by-assay basis by a single pathologist trained in all methods, in a Clinical Laboratory Improvements Amendments program-certified laboratory. An additional pathologist performed an independent review of 200 stained samples for each assay.Results:PD-L1 expression was evaluable with all assays in 493 samples. The three assays showed similar patterns of tumor membrane staining, with high correlation between percent PD-L1 staining. An overall percentage agreement of >90% was achieved between assays at multiple expression cutoffs, including 1%, 10%, 25%, and 50% tumor membrane staining.Conclusions:This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked.Clin Cancer Res; 23(14); 3585-91. ©2017 AACR.
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, United Kingdom. marianne.ratcliffe@astrazeneca.com.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Ratcliffe
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Sharpe
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, United Kingdom.
authors.forename: Anita
authors.initials: A
authors.lastname: Midha
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, United Kingdom.
authors.forename: Craig
authors.initials: C
authors.lastname: Barker
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, United Kingdom.
authors.forename: Marietta
authors.initials: M
authors.lastname: Scott
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Scorer
authors.affiliation: Hematogenix, Tinley Park, Illinois.
authors.forename: Hytham
authors.initials: H
authors.lastname: Al-Masri
authors.affiliation: Translational Medicine, MedImmune, Gaithersburg, Maryland.
authors.forename: Marlon C
authors.initials: MC
authors.lastname: Rebelatto
authors.affiliation: Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D060890:B7-H1 Antigen / Q000191:economics / Q000235:genetics* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D005557:Formaldehyde; C000613593:durvalumab; D000077594:Nivolumab; C582435:pembrolizumab