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. (May 2019)

• Record Type: Journal Article
• Authors: Kerr, Keith M.; Thunnissen, Erik; Dafni, Urania; Finn, Stephen P.; Bubendorf, Lukas; Soltermann, Alex; Verbeken, Eric; Biernat, Wojciech; Warth, Arne; Marchetti, Antonio; Speel, Ernst-Jan M.; Pokharel, Sarawati; Quinn, Anne Marie; Monkhorst, Kim; Navarro, Atilio; Madsen, Line Bille; Radonic, Teodora; Wilson, Joan; De Luca, Graziano; Gray, Steven G.; Cheney, Richard; Savic, Spasenija; Martorell, Miguel; Muley, Thomas; Baas, Paul; Meldgaard, Peter; Blackhall, Fiona; Dingemans, Anne-Marie; Dziadziuszko, Rafal; Vansteenkiste, Johan; Weder, Walter; Polydoropoulou, Varvara; Geiger, Thomas; Kammler, Roswitha; Peters, Solange; Stahel, Rolf;
• Is Part Of: Lung cancer. Volume 131(2019)
• Page Start: 95
• Page End: 103
• Publication Date: 2019-05
• Subjects: Non-small cell lung cancer -- PD-L1; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.03.012
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: A cohort study of surgically resected, stage I-III NSCLC cases from 15 centers. PD-L1 expression was assessed in 2182 NSCLC cases. PD-L1 positivity is associated with a better prognosis for adenocarcinoma patients. 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.