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A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer

BACKGROUND: This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique. METHODS: This retrospective...

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Autores principales: Abedian Kalkhoran, Hanieh, Zwaveling, Juliëtte, Storm, Bert N., van Laar, Sylvia A., Portielje, Johanneke EA, Codrington, Henk, Luijten, Dieuwke, Brocken, Pepijn, Smit, Egbert F., Visser, Loes E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015929/
https://www.ncbi.nlm.nih.gov/pubmed/36918817
http://dx.doi.org/10.1186/s12885-023-10701-z
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author Abedian Kalkhoran, Hanieh
Zwaveling, Juliëtte
Storm, Bert N.
van Laar, Sylvia A.
Portielje, Johanneke EA
Codrington, Henk
Luijten, Dieuwke
Brocken, Pepijn
Smit, Egbert F.
Visser, Loes E.
author_facet Abedian Kalkhoran, Hanieh
Zwaveling, Juliëtte
Storm, Bert N.
van Laar, Sylvia A.
Portielje, Johanneke EA
Codrington, Henk
Luijten, Dieuwke
Brocken, Pepijn
Smit, Egbert F.
Visser, Loes E.
author_sort Abedian Kalkhoran, Hanieh
collection PubMed
description BACKGROUND: This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique. METHODS: This retrospective study included patients with stage III/IV NSCLC treated with a PD-(L)1 inhibitor (nivolumab, pembrolizumab, atezolizumab and durvalumab) at Leiden University Medical Centre and Haga Teaching hospital, (both in The Netherlands) from September 2016 to May 2021. All the relevant data was extracted from the structured and unstructured fields of the Electronic Health Records using a novel text-mining tool. Effectiveness [progression-free survival (PFS) and overall survival (OS)] and safety (the incidence of nine potentially fatal irAEs and systemic corticosteroid requirement) outcomes were compared across age subgroups (young: < 65 years, Middle-aged: 65–74 years, and old: ≥ 75 years) after adjustment for confounding. RESULTS: Of 689 patients, 310 patients (45.0%) were < 65 years, 275 patients (39.9%) were aged between 65 and 74 years, and 104 patients (15.1%) were ≥ 75 years. There was no significant difference between younger and older patients regarding PFS (median PFS 12, 8, 13 months respectively; Hazard ratio (HR)(middle-aged) = 1.14, 95% CI 0.92–1.41; HR(old) = 1.10, 95% CI 0.78–1.42). This was also the case for OS (median OS 19, 14, 18 months respectively; HR(middle-aged) = 1.22, 95% CI 0.96–1.53; HR(old) = 1.10, 95% CI 0.79–1.52). Safety analysis demonstrated a higher incidence of pneumonitis among patients aged 65–74. When all the investigated irAEs were pooled, there was no statistically significant difference found between age and the incidence of potentially fatal irAEs. CONCLUSIONS: The use of PD-(L)1 inhibitors is not associated with age related decrease of PFS and OS, nor with increased incidence of serious irAEs compared to younger patients receiving these treatments. Chronological age must therefore not be used as a predictor for the effectiveness or safety of ICIs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10701-z.
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spelling pubmed-100159292023-03-16 A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer Abedian Kalkhoran, Hanieh Zwaveling, Juliëtte Storm, Bert N. van Laar, Sylvia A. Portielje, Johanneke EA Codrington, Henk Luijten, Dieuwke Brocken, Pepijn Smit, Egbert F. Visser, Loes E. BMC Cancer Research BACKGROUND: This study was designed to investigate the impact of age on the effectiveness and immune-related adverse events (irAEs) of programmed death-(ligand)1 [PD-(L)1] inhibitors in patients with non-small cell lung cancer (NSCLC) using a novel text-mining technique. METHODS: This retrospective study included patients with stage III/IV NSCLC treated with a PD-(L)1 inhibitor (nivolumab, pembrolizumab, atezolizumab and durvalumab) at Leiden University Medical Centre and Haga Teaching hospital, (both in The Netherlands) from September 2016 to May 2021. All the relevant data was extracted from the structured and unstructured fields of the Electronic Health Records using a novel text-mining tool. Effectiveness [progression-free survival (PFS) and overall survival (OS)] and safety (the incidence of nine potentially fatal irAEs and systemic corticosteroid requirement) outcomes were compared across age subgroups (young: < 65 years, Middle-aged: 65–74 years, and old: ≥ 75 years) after adjustment for confounding. RESULTS: Of 689 patients, 310 patients (45.0%) were < 65 years, 275 patients (39.9%) were aged between 65 and 74 years, and 104 patients (15.1%) were ≥ 75 years. There was no significant difference between younger and older patients regarding PFS (median PFS 12, 8, 13 months respectively; Hazard ratio (HR)(middle-aged) = 1.14, 95% CI 0.92–1.41; HR(old) = 1.10, 95% CI 0.78–1.42). This was also the case for OS (median OS 19, 14, 18 months respectively; HR(middle-aged) = 1.22, 95% CI 0.96–1.53; HR(old) = 1.10, 95% CI 0.79–1.52). Safety analysis demonstrated a higher incidence of pneumonitis among patients aged 65–74. When all the investigated irAEs were pooled, there was no statistically significant difference found between age and the incidence of potentially fatal irAEs. CONCLUSIONS: The use of PD-(L)1 inhibitors is not associated with age related decrease of PFS and OS, nor with increased incidence of serious irAEs compared to younger patients receiving these treatments. Chronological age must therefore not be used as a predictor for the effectiveness or safety of ICIs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10701-z. BioMed Central 2023-03-14 /pmc/articles/PMC10015929/ /pubmed/36918817 http://dx.doi.org/10.1186/s12885-023-10701-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Abedian Kalkhoran, Hanieh
Zwaveling, Juliëtte
Storm, Bert N.
van Laar, Sylvia A.
Portielje, Johanneke EA
Codrington, Henk
Luijten, Dieuwke
Brocken, Pepijn
Smit, Egbert F.
Visser, Loes E.
A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer
title A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer
title_full A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer
title_fullStr A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer
title_full_unstemmed A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer
title_short A text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of PD-1 and PD-L1 inhibitors in older patients with stage III/IV non-small cell lung cancer
title_sort text-mining approach to study the real-world effectiveness and potentially fatal immune-related adverse events of pd-1 and pd-l1 inhibitors in older patients with stage iii/iv non-small cell lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015929/
https://www.ncbi.nlm.nih.gov/pubmed/36918817
http://dx.doi.org/10.1186/s12885-023-10701-z
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