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

Keith M. Kerr; Erik Thunnissen; Urania Dafni; Stephen P. Finn; Lukas Bubendorf; Alex Soltemiann; Eric Verbeken; Wojciech Biernat; Arne Warth; Antonio Marchetti; Ernst-Jan M. Speel; Sarawati Pokharel; Anne Marie Quinn; Kim Monlchorst; Atilio Navarro; Line Bille Madsen; Teodora Radonic; Joan Wilson; Graziano De Luca; Steven G. Gray; Richard Cheney; Spasenija Savic; Miguel Martorell; Thomas Muley; Paul Baas; Peter Meldgaard; Fiona Blackhall; Anne-Marie Dingemans; Rafal Dziadziuszko; Johan Vansteenkiste; Walter Weder; Varvara Polydoropoulou; Thomas Geiger; Roswitha Kammler; Solange Peters; Rolf Stahel; Rafael Rosell; Fiona Blackhall; Urania Dafni; Miguel Angel Molina; Lukas Bubendorf; Erik Thunnissen; Stephen Finn; Anita Hiltbrunner; Egbert Smit; Saraswati Pokharel; Lungscape Consortium

doi:10.1016/j.lungcan.2019.03.012

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

Keith M. Kerr^*, Erik Thunnissen, Urania Dafni, Stephen P. Finn, Lukas Bubendorf, Alex Soltemiann, Eric Verbeken, Wojciech Biernat, Arne Warth, Antonio Marchetti, Ernst-Jan M. Speel, Sarawati Pokharel, Anne Marie Quinn, Kim Monlchorst, Atilio Navarro, Line Bille Madsen, Teodora Radonic, Joan Wilson, Graziano De Luca, Steven G. GrayRichard Cheney, Spasenija Savic, Miguel Martorell, Thomas Muley, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Rafal Dziadziuszko, Johan Vansteenkiste, Walter Weder, Varvara Polydoropoulou, Thomas Geiger, Roswitha Kammler, Solange Peters, Rolf Stahel, Rafael Rosell, Fiona Blackhall, Urania Dafni, Miguel Angel Molina, Lukas Bubendorf, Erik Thunnissen, Stephen Finn, Anita Hiltbrunner, Egbert Smit, Saraswati Pokharel, Lungscape Consortium

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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-Ll positivity is linked to a poor prognosis, others suggest that PD-Ll 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 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 FD-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-Ll positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

Original language	English
Pages (from-to)	95-103
Number of pages	9
Journal	Lung Cancer
Volume	131
DOIs	https://doi.org/10.1016/j.lungcan.2019.03.012
Publication status	Published - May 2019

Keywords

Non-small cell lung cancer
PD-L1
CELL LUNG-CANCER
DEATH-LIGAND 1
CLINICOPATHOLOGICAL ANALYSIS
PROGNOSTIC-SIGNIFICANCE
EXPRESSION
ADENOCARCINOMA
OVEREXPRESSION
AMPLIFICATION
INHIBITORS
MUTATIONS

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10.1016/j.lungcan.2019.03.012

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Kerr, K. M., Thunnissen, E., Dafni, U., Finn, S. P., Bubendorf, L., Soltemiann, A., Verbeken, E., Biernat, W., Warth, A., Marchetti, A., Speel, E.-J. M., Pokharel, S., Quinn, A. M., Monlchorst, K., Navarro, A., Madsen, L. B., Radonic, T., Wilson, J., De Luca, G., ... Lungscape Consortium (2019). 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. Lung Cancer, 131, 95-103. https://doi.org/10.1016/j.lungcan.2019.03.012

@article{de07d30e80c64911bc614315eb3abeb7,

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-Ll positivity is linked to a poor prognosis, others suggest that PD-Ll 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 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 FD-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-Ll positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.",

keywords = "Non-small cell lung cancer, PD-L1, CELL LUNG-CANCER, DEATH-LIGAND 1, CLINICOPATHOLOGICAL ANALYSIS, PROGNOSTIC-SIGNIFICANCE, EXPRESSION, ADENOCARCINOMA, OVEREXPRESSION, AMPLIFICATION, INHIBITORS, MUTATIONS",

author = "Kerr, {Keith M.} and Erik Thunnissen and Urania Dafni and Finn, {Stephen P.} and Lukas Bubendorf and Alex Soltemiann 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 Monlchorst 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 and Rafael Rosell and Fiona Blackhall and Urania Dafni and Molina, {Miguel Angel} and Lukas Bubendorf and Erik Thunnissen and Stephen Finn and Anita Hiltbrunner and Egbert Smit and Saraswati Pokharel and {Lungscape Consortium}",

note = "Funding Information: This translational research study was funded by Bristol-Myers Squibb . Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2019",

month = may,

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",

}

Kerr, KM, Thunnissen, E, Dafni, U, Finn, SP, Bubendorf, L, Soltemiann, A, Verbeken, E, Biernat, W, Warth, A, Marchetti, A, Speel, E-JM, Pokharel, S, Quinn, AM, Monlchorst, K, Navarro, A, Madsen, LB, Radonic, T, Wilson, J, De Luca, G, Gray, SG, 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, Rosell, R, Blackhall, F, Dafni, U, Molina, MA, Bubendorf, L, Thunnissen, E, Finn, S, Hiltbrunner, A, Smit, E, Pokharel, S & Lungscape Consortium 2019, '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', Lung Cancer, vol. 131, pp. 95-103. https://doi.org/10.1016/j.lungcan.2019.03.012

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. / Kerr, Keith M.; Thunnissen, Erik; Dafni, Urania et al.
In: Lung Cancer, Vol. 131, 05.2019, p. 95-103.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC

T2 - Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project

AU - Kerr, Keith M.

AU - Thunnissen, Erik

AU - Dafni, Urania

AU - Finn, Stephen P.

AU - Bubendorf, Lukas

AU - Soltemiann, 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 - Monlchorst, 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

AU - Rosell, Rafael

AU - Blackhall, Fiona

AU - Dafni, Urania

AU - Molina, Miguel Angel

AU - Bubendorf, Lukas

AU - Thunnissen, Erik

AU - Finn, Stephen

AU - Hiltbrunner, Anita

AU - Smit, Egbert

AU - Pokharel, Saraswati

AU - Lungscape Consortium

PY - 2019/5

Y1 - 2019/5

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-Ll positivity is linked to a poor prognosis, others suggest that PD-Ll 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 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 FD-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-Ll 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-Ll positivity is linked to a poor prognosis, others suggest that PD-Ll 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 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 FD-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-Ll positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

KW - Non-small cell lung cancer

KW - PD-L1

KW - CELL LUNG-CANCER

KW - DEATH-LIGAND 1

KW - CLINICOPATHOLOGICAL ANALYSIS

KW - PROGNOSTIC-SIGNIFICANCE

KW - EXPRESSION

KW - ADENOCARCINOMA

KW - OVEREXPRESSION

KW - AMPLIFICATION

KW - INHIBITORS

KW - MUTATIONS

U2 - 10.1016/j.lungcan.2019.03.012

DO - 10.1016/j.lungcan.2019.03.012

M3 - Article

SN - 0169-5002

VL - 131

SP - 95

EP - 103

JO - Lung Cancer

JF - Lung Cancer

ER -