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

Lungscape Consortium

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Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusion: PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.
Original languageEnglish
Pages (from-to)95-103
JournalLung Cancer
Volume131
DOIs
Publication statusPublished - 2019

Cite this

@article{9425a69896804c17ad62c1c4c4de24de,
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",
abstract = "Introduction: 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. Methods: 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. Results: 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. Conclusion: PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.",
author = "{Lungscape Consortium} and Kerr, {Keith M.} and Erik Thunnissen and Urania Dafni and Finn, {Stephen P.} and Lukas Bubendorf and Alex Soltermann and Eric Verbeken and Wojciech Biernat and Arne Warth and Antonio Marchetti and Speel, {Ernst-Jan M.} and Sarawati Pokharel and Quinn, {Anne Marie} and Kim Monkhorst and Atilio Navarro and Madsen, {Line Bille} and Teodora Radonic and Joan Wilson and {de Luca}, Graziano and Gray, {Steven G.} and Richard Cheney and Spasenija Savic and Miguel Martorell and Thomas Muley and Paul Baas and Peter Meldgaard and Fiona Blackhall and Anne-Marie Dingemans and Rafal Dziadziuszko and Johan Vansteenkiste and Walter Weder and Varvara Polydoropoulou and Thomas Geiger and Roswitha Kammler and Solange Peters and Rolf Stahel",
year = "2019",
doi = "10.1016/j.lungcan.2019.03.012",
language = "English",
volume = "131",
pages = "95--103",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - 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

AU - Lungscape Consortium

AU - Kerr, Keith M.

AU - Thunnissen, Erik

AU - Dafni, Urania

AU - Finn, Stephen P.

AU - Bubendorf, Lukas

AU - Soltermann, Alex

AU - Verbeken, Eric

AU - Biernat, Wojciech

AU - Warth, Arne

AU - Marchetti, Antonio

AU - Speel, Ernst-Jan M.

AU - Pokharel, Sarawati

AU - Quinn, Anne Marie

AU - Monkhorst, Kim

AU - Navarro, Atilio

AU - Madsen, Line Bille

AU - Radonic, Teodora

AU - Wilson, Joan

AU - de Luca, Graziano

AU - Gray, Steven G.

AU - Cheney, Richard

AU - Savic, Spasenija

AU - Martorell, Miguel

AU - Muley, Thomas

AU - Baas, Paul

AU - Meldgaard, Peter

AU - Blackhall, Fiona

AU - Dingemans, Anne-Marie

AU - Dziadziuszko, Rafal

AU - Vansteenkiste, Johan

AU - Weder, Walter

AU - Polydoropoulou, Varvara

AU - Geiger, Thomas

AU - Kammler, Roswitha

AU - Peters, Solange

AU - Stahel, Rolf

PY - 2019

Y1 - 2019

N2 - Introduction: 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. Methods: 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. Results: 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. Conclusion: PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

AB - Introduction: 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. Methods: 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. Results: 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. Conclusion: PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063438070&origin=inward

U2 - 10.1016/j.lungcan.2019.03.012

DO - 10.1016/j.lungcan.2019.03.012

M3 - Article

VL - 131

SP - 95

EP - 103

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -