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Translational research

3780 - Association of programmed cell death 1 ligand (PD-L1) expression with molecular alterations in non-small cell lung cancer (NSCLC) patients (pts): Results from the European Thoracic Oncology Platform (ETOP) Lungscape cohort

Date

09 Sep 2017

Session

Translational research

Presenters

Keith Kerr

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

K.M. Kerr1, E. Thunnissen2, U. Dafni3, A. Soltermann4, S. Finn5, L. Bubendorf6, E. Verbeken7, W. Biernat8, A. Warth9, A. Marchetti10, E. Speel11, S. Pokharel12, A.M. Quinn13, K. Monkhorst14, A. Navarro15, V. Polydoropoulou16, R. Kammler17, S. Peters18, R.A. Stahel19, O.B. Lungscape Consortium20

Author affiliations

  • 1 Department Of Pathology, Aberdeen Royal Infirmary, AB25 2ZN - Aberdeen/GB
  • 2 Pathology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 3 University Of Athens, FSF-H, ETOP Statistical Center, 115 27 - Athens/GR
  • 4 Pathology And Molecular Pathology, University Hospital Zurich, Zurich/CH
  • 5 Cancer Molecular Diagnostics, St James's Hospital, 8 - Dublin/IE
  • 6 Institute Of Pathology, University Hospital Basel, 4031 - Basel/CH
  • 7 Department Of Human Genetics, University Hospital KU Leuven, Leuven/BE
  • 8 Department Of Pathology, Medical University of Gdansk, Gdansk/PL
  • 9 Department Of Molecular Pathology + Translational Lung Research Center Heidelberg, University Medical Center, 69120 - Heidelberg/DE
  • 10 Center Of Predictive Molecular Medicine, CeSI-MeT, University of Chieti, Chieti/IT
  • 11 Grow School For Oncology And Developmental Biology, Department Of Pathology, Maastricht University Medical Center (MUMC), P.O. Box 616 - Maastricht/NL
  • 12 Department Of Pathology, Roswell Park Cancer Institute, Buffalo/US
  • 13 Cellular Pathology, University Hospital South Manchester, Wythenshawe/GB
  • 14 Department Of Pathology, Netherlands Cancer Institute, Amsterdam/NL
  • 15 Department Of Pathology, General University Hospital Research, Valencia/ES
  • 16 Etop Statistical Center, FSF-H, 115 27 - Athens/GR
  • 17 Translational Research Coordination, ETOP - European Thoracic Oncology Platform, 3008 - Bern/CH
  • 18 Oncology, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 19 Laboratory Of Molecular Oncology, Department Of Oncology, University Hospital Zürich, Zürich/CH
  • 20 Translational Research, ETOP - European Thoracic Oncology Platform, 3008 - Bern/CH
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Abstract 3780

Background

PD-L1 is the only validated predictive biomarker for use with immune checkpoint inhibitors targeting the PD-1 pathway in advanced NSCLC.

Methods

Correlation of PD-L1 expression with that of MET, ALK, PTEN proteins by IHC (MET+:≥2+ and % staining≥50%, ALK+: ≥1+, PTEN+: H-score>0) and mutations in KRAS, EGFR, PIK3CA or MET genes was explored in the large international ETOP Lungscape cohort of resected, stages I–III, NSCLC. The DAKO 28-8 immunohistochemistry assay was used to assess PD-L1 expression, and gene mutations testing was based on Fluidigm technology, a microfluidics-based multiplex PCR platform. PD-L1 expression was defined with alternative cut-offs (≥1%, 5%, 50%) for neoplastic cell membrane staining.

Results

PD-L1 expression was assessed in 2182 pts, from 15 centers, 51/42/7% adenocarcinomas (AC)/squamous cell carcinoma (SCC)/other, 49/29/22% stage I/II/III, 32/54/11% current/former/never smokers, 4% unknown smoking status. For the 1% cut-off, a significant association was detected between PD-L1 and MET expression both for AC and SCC (PD-L1 positivity in AC: 61% in MET + vs 33% in MET-, p 

Conclusions

In this large NSCLC cohort, PD-L1 positivity (with 1%, 5% or 50% cut-off) is found to be significantly associated with IHC MET overexpression, expression of PTEN and KRAS mutation.

Clinical trial identification

Legal entity responsible for the study

European Thoracic Oncology Platform (ETOP)

Funding

Brystol-Myers Squibb International Corporation

Disclosure

K.M. Kerr: Consulting or advisory role and paid participation in a speakers’ bureau: Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche. L. Bubendorf: Member of advisory boards: BI, MSD, Roche K. Monkhorst: Member of 4 advisory boards: Pfizer, Roche, MSD, BMS All other authors have declared no conflicts of interest.

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