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High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy

PURPOSE: Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 ex...

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Autores principales: Yoon, Byung Woo, Chang, Boksoon, Lee, Seung Hyeun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445533/
https://www.ncbi.nlm.nih.gov/pubmed/32903896
http://dx.doi.org/10.2147/OTT.S271011
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author Yoon, Byung Woo
Chang, Boksoon
Lee, Seung Hyeun
author_facet Yoon, Byung Woo
Chang, Boksoon
Lee, Seung Hyeun
author_sort Yoon, Byung Woo
collection PubMed
description PURPOSE: Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by the analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group. RESULTS: Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ≥ 50%, 1–49%, and <1%, was 17.6%, 32.8%, and 49.6%, respectively. The RR was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (43.5% vs 72.1% vs 78.5%, all p = 0.001). In multivariate analysis, PD-L1 TPS ≥ 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004) and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%. In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (13.3% vs 40.0% vs 53.3%, all p = 0.001). PD-L1 TPS ≥ 50% was an independent predictor of a lower frequency of this mutation (HR = 0.63, p = 0.043). CONCLUSION: High PD-L1 expression was associated with unfavorable clinical outcome and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach.
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spelling pubmed-74455332020-09-04 High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy Yoon, Byung Woo Chang, Boksoon Lee, Seung Hyeun Onco Targets Ther Original Research PURPOSE: Although programmed death-ligand 1 (PD-L1) expression is widely accepted as a predictive and prognostic biomarker in immunotherapy, its implications in lung cancer patients with driving mutations are still unclear. The objective of this study is to determine the association between PD-L1 expression and treatment outcome in epidermal growth factor receptor (EGFR)-mutated lung cancer treated with tyrosine kinase inhibitors (TKIs). METHODS: We retrospectively enrolled EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD-L1 tumor proportion score (TPS) using the 22C3 pharmDx assay. We investigated the distribution of patients with different PD-L1 TPS values, followed by the analysis of response rate (RR), survival rate, and incidence of secondary T790M mutation according to the PD-L1 TPS group. RESULTS: Among the 131 patients analyzed, the proportion of patients with PD-L1 TPS ≥ 50%, 1–49%, and <1%, was 17.6%, 32.8%, and 49.6%, respectively. The RR was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (43.5% vs 72.1% vs 78.5%, all p = 0.001). In multivariate analysis, PD-L1 TPS ≥ 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004) and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%. In addition, the frequency of secondary T790M mutation after TKI failure was significantly lower in the group with PD-L1 TPS ≥ 50% than in the other groups (13.3% vs 40.0% vs 53.3%, all p = 0.001). PD-L1 TPS ≥ 50% was an independent predictor of a lower frequency of this mutation (HR = 0.63, p = 0.043). CONCLUSION: High PD-L1 expression was associated with unfavorable clinical outcome and less development of secondary T790M mutation, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach. Dove 2020-08-20 /pmc/articles/PMC7445533/ /pubmed/32903896 http://dx.doi.org/10.2147/OTT.S271011 Text en © 2020 Yoon et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Yoon, Byung Woo
Chang, Boksoon
Lee, Seung Hyeun
High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
title High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
title_full High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
title_fullStr High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
title_full_unstemmed High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
title_short High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy
title_sort high pd-l1 expression is associated with unfavorable clinical outcome in egfr-mutated lung adenocarcinomas treated with targeted therapy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445533/
https://www.ncbi.nlm.nih.gov/pubmed/32903896
http://dx.doi.org/10.2147/OTT.S271011
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