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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, K Thunnissen, E Dafni, U Finn, SP Bubendorf, L Soltermann, A Verbeken, E Biernat, W Warth, A Marchetti, A
Kerr, K
Thunnissen, E
Dafni, U
Finn, SP
Bubendorf, L
Soltermann, A
Verbeken, E
Biernat, W
Warth, A
Marchetti, A
Citations
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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.
Authors
Kerr, K
Thunnissen, E
Dafni, U
Finn, SP
Bubendorf, L
Soltermann, A
Verbeken, E
Biernat, W
Warth, A
Marchetti, A
Speel, E
Pokharel, S
Quinn, A
Monkhorst, K
Navarro, A
Madsen, L
Radonic, T
Wilson, J
De Luca, G
Gray, S
Cheney, R
Savic, S
Martorell, M
Muley, T
Baas, P
Meldgaard, P
Blackhall, Fiona H
Dingemans, A
Dziadziuszko, R
Vansteenkiste, J
Weder, W
Polydoropoulou, V
Geiger, T
Kammler, R
Peters, S
Stahel, R
Thunnissen, E
Dafni, U
Finn, SP
Bubendorf, L
Soltermann, A
Verbeken, E
Biernat, W
Warth, A
Marchetti, A
Speel, E
Pokharel, S
Quinn, A
Monkhorst, K
Navarro, A
Madsen, L
Radonic, T
Wilson, J
De Luca, G
Gray, S
Cheney, R
Savic, S
Martorell, M
Muley, T
Baas, P
Meldgaard, P
Blackhall, Fiona H
Dingemans, A
Dziadziuszko, R
Vansteenkiste, J
Weder, W
Polydoropoulou, V
Geiger, T
Kammler, R
Peters, S
Stahel, R
Description
Date
2019
Publisher
Collections
Keywords
Type
Article
Citation
Kerr KM, Thunnissen E, Dafni U, Finn SP, Bubendorf L, Soltermann A, et al. 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. 2019; 131:95-103.