A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project.

Details

Serval ID
serval:BIB_C471070F0828
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project.
Journal
Lung cancer
Author(s)
Kerr K.M., Thunnissen E., Dafni U., Finn S.P., Bubendorf L., Soltermann A., Verbeken E., Biernat W., Warth A., Marchetti A., Speel E.M., Pokharel S., Quinn A.M., Monkhorst K., Navarro A., Madsen L.B., Radonic T., Wilson J., De Luca G., Gray S.G., Cheney R., Savic S., Martorell M., Muley T., Baas P., Meldgaard P., Blackhall F., Dingemans A.M., Dziadziuszko R., Vansteenkiste J., Weder W., Polydoropoulou V., Geiger T., Kammler R., Peters S., Stahel R.
Working group(s)
Lungscape Consortium
ISSN
1872-8332 (Electronic)
ISSN-L
0169-5002
Publication state
Published
Issued date
05/2019
Peer-reviewed
Oui
Volume
131
Pages
95-103
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis.
PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining.
PD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p < 0.001, 5%/25%/50% cut-offs) and SCC (p < 0.001, 5% & 50% cut-offs and p = 0.0017 for 25%). When adjusting for clinicopathological characteristics, a significant prognostic effect was identified in adenocarcinomas (adjusted p-values: 0.024/0.064/0.063 for RFS/TTR/OS 1% cut-off, analogous for 5%/25%, but not for 50%). Similar results obtained for the model including all histologies, but no effect was found for the squamous cell carcinomas.
PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.
Keywords
Adenocarcinoma of Lung/diagnosis, Adenocarcinoma of Lung/metabolism, Adenocarcinoma of Lung/mortality, Adult, Aged, Aged, 80 and over, B7-H1 Antigen/metabolism, Biomarkers, Tumor/metabolism, Carcinoma, Non-Small-Cell Lung/diagnosis, Carcinoma, Non-Small-Cell Lung/metabolism, Carcinoma, Non-Small-Cell Lung/mortality, Cohort Studies, Europe, Follow-Up Studies, Humans, Immunotherapy/methods, Lung Neoplasms/diagnosis, Lung Neoplasms/metabolism, Lung Neoplasms/mortality, Male, Middle Aged, Neoplasm Staging, Prognosis, Proto-Oncogene Proteins c-met/metabolism, Retrospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Non-small cell lung cancer, PD-L1
Pubmed
Web of science
Create date
13/05/2019 7:40
Last modification date
28/02/2020 6:19
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