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 -