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Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non-Small-Cell Lung Cancer

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  1. The prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer in an unselected, consecutive population

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  • Reinhard Büttner
  • John R Gosney
  • Birgit Guldhammer Skov
  • Julien Adam
  • Noriko Motoi
  • Kenneth J Bloom
  • Manfred Dietel
  • John W Longshore
  • Fernando López-Ríos
  • Frédérique Penault-Llorca
  • Giuseppe Viale
  • Andrew C Wotherspoon
  • Keith M Kerr
  • Ming-Sound Tsao
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Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and Drug Administration-cleared complementary PD-L1 tests are available for both. PD-L1 IHC assays used to assess PD-L1 expression in patients treated with programmed death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28-8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1 SP263 (SP263). Differences in antibodies and IHC platforms have raised questions about comparability among these assays and their diagnostic use. This review provides practical information to help physicians and pathologists understand analytical features and comparability of various PD-L1 IHC assays and their diagnostic use. Methods We reviewed and summarized published or otherwise reported studies (January 2016 to January 2017) on clinical trial and laboratory-developed PD-L1 IHC assays (LDAs). Studies assessing the effect of diagnostic methods on PD-L1 expression levels were analyzed to address practical issues related to tissue samples used for testing. Results High concordance and interobserver reproducibility were observed with the 28-8, 22C3, and SP263 clinical trial assays for PD-L1 expression on tumor cell membranes, whereas lower PD-L1 expression was detected with SP142. Immune-cell PD-L1 expression was variable and interobserver concordance was poor. Inter- and intratumoral heterogeneity had variable effects on PD-L1 expression. Concordance among LDAs was variable. Conclusion High concordance among 28-8, 22C3, and SP263 when assessing PD-L1 expression on tumor cell membranes suggests possible interchangeability of their clinical use for NSCLC but not for assessment of PD-L1 expression on immune cells. Development of LDAs requires stringent standardization before their recommendation for routine clinical use.

Original languageEnglish
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume35
Issue number34
Pages (from-to)3867-3876
Number of pages10
ISSN0732-183X
DOIs
Publication statusPublished - 1 Dec 2017

    Research areas

  • Antibodies, Monoclonal/administration & dosage, Antibodies, Monoclonal, Humanized/administration & dosage, B7-H1 Antigen/genetics, Biopsy, Needle, Carcinoma, Non-Small-Cell Lung/drug therapy, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Lung Neoplasms/drug therapy, Male, Molecular Targeted Therapy/methods, Nivolumab, Prognosis, Risk Assessment, Survival Rate, Treatment Outcome

ID: 56411214