Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy

Introduction: Poly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed cell deathligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti-programmed cell death protein 1-based therapies in patients with metastatic squamous NSCL...

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Autores: Hochmair, Maximilian, Schenker, Michael, Cobo Dols, Manuel, Kim, Tae Min, Ozyilkan, Ozgur, Smagina, Maria, Leonova, Viktoriya, Kato, Terufumi, Fedenko, Alexander, Angelis, Flavia de, Rittmeyer, Achim, Gray, Jhanelle E., Greystoke, Alastair, Aggarwal, Himani, Huang, Qinlei, Zhao, Bin, Lara Guerra, Humberto, Nadal, Ernest
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/221370
Acceso en línea:https://hdl.handle.net/2445/221370
Access Level:acceso abierto
Palabra clave:Anticossos monoclonals
Càncer de pulmó
Quimioteràpia
Monoclonal antibodies
Lung cancer
Chemotherapy
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spelling Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus ChemotherapyHochmair, MaximilianSchenker, MichaelCobo Dols, ManuelKim, Tae MinOzyilkan, OzgurSmagina, MariaLeonova, ViktoriyaKato, TerufumiFedenko, AlexanderAngelis, Flavia deRittmeyer, AchimGray, Jhanelle E.Greystoke, AlastairAggarwal, HimaniHuang, QinleiZhao, BinLara Guerra, HumbertoNadal, ErnestAnticossos monoclonalsCàncer de pulmóQuimioteràpiaMonoclonal antibodiesLung cancerChemotherapyIntroduction: Poly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed cell deathligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti-programmed cell death protein 1-based therapies in patients with metastatic squamous NSCLC. Methods: In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received four cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo. Dual primary end points were progression- free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (the final PFS analysis); OS was tested at final analysis. Results: A total of 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo. At interim analysis 2, with median follow-up of 27.1 months, median (95% confidence interval [CI]) PFS was 8.3 (6.7-9.7) months in the pembrolizumab plus olaparib group and 5.4 (4.1-5.6) months in the pembrolizumab plus placebo group (hazard ratio = 0.77, 95% CI: 0.63-0.93, p = 0.0040 [not significant at a one-sided superiority boundary of p = 0.003]). At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9-22.2) and 18.6 (16.0-21.6) months, respectively (hazard ratio = 1.01, 95% CI: 0.83-1.24, p = 0.5481). Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively. Conclusions: Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo; neither PFS nor OS met the prespecified statistical significance boundary. No new safety signals were identified. Trial registration: ClinicalTrials.gov, NCT03976362. (c) 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and The Author(s). Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).Elsevier BV2025202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/221370Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.jtho.2024.10.012Journal of Thoracic Oncology, 2025, vol. 20, num. 2, p. 203-218https://doi.org/10.1016/j.jtho.2024.10.012cc-by-nc-nd (c) Hochmair et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2213702026-05-29T05:05:01Z
dc.title.none.fl_str_mv Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
title Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
spellingShingle Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
Hochmair, Maximilian
Anticossos monoclonals
Càncer de pulmó
Quimioteràpia
Monoclonal antibodies
Lung cancer
Chemotherapy
title_short Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
title_full Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
title_fullStr Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
title_full_unstemmed Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
title_sort Pembrolizumab With or Without Maintenance Olaparib for Metastatic Squamous Non–Small-Cell Lung Cancer That Responded to First-Line Pembrolizumab Plus Chemotherapy
dc.creator.none.fl_str_mv Hochmair, Maximilian
Schenker, Michael
Cobo Dols, Manuel
Kim, Tae Min
Ozyilkan, Ozgur
Smagina, Maria
Leonova, Viktoriya
Kato, Terufumi
Fedenko, Alexander
Angelis, Flavia de
Rittmeyer, Achim
Gray, Jhanelle E.
Greystoke, Alastair
Aggarwal, Himani
Huang, Qinlei
Zhao, Bin
Lara Guerra, Humberto
Nadal, Ernest
author Hochmair, Maximilian
author_facet Hochmair, Maximilian
Schenker, Michael
Cobo Dols, Manuel
Kim, Tae Min
Ozyilkan, Ozgur
Smagina, Maria
Leonova, Viktoriya
Kato, Terufumi
Fedenko, Alexander
Angelis, Flavia de
Rittmeyer, Achim
Gray, Jhanelle E.
Greystoke, Alastair
Aggarwal, Himani
Huang, Qinlei
Zhao, Bin
Lara Guerra, Humberto
Nadal, Ernest
author_role author
author2 Schenker, Michael
Cobo Dols, Manuel
Kim, Tae Min
Ozyilkan, Ozgur
Smagina, Maria
Leonova, Viktoriya
Kato, Terufumi
Fedenko, Alexander
Angelis, Flavia de
Rittmeyer, Achim
Gray, Jhanelle E.
Greystoke, Alastair
Aggarwal, Himani
Huang, Qinlei
Zhao, Bin
Lara Guerra, Humberto
Nadal, Ernest
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Anticossos monoclonals
Càncer de pulmó
Quimioteràpia
Monoclonal antibodies
Lung cancer
Chemotherapy
topic Anticossos monoclonals
Càncer de pulmó
Quimioteràpia
Monoclonal antibodies
Lung cancer
Chemotherapy
description Introduction: Poly (adenosine diphosphate-ribose) polymerase inhibitors can up-regulate programmed cell deathligand 1 expression and promote immune-mediated responses and may improve efficacy of first-line anti-programmed cell death protein 1-based therapies in patients with metastatic squamous NSCLC. Methods: In this randomized, double-blind, phase 3 trial (NCT03976362), adults with previously untreated stage IV squamous NSCLC received four cycles of induction therapy (pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel or nab-paclitaxel). Patients with disease control were randomized to 31 cycles of pembrolizumab 200 mg every 3 weeks plus olaparib 300 mg orally twice daily or placebo. Dual primary end points were progression- free survival (PFS) and overall survival (OS). PFS was tested at interim analysis 2 (the final PFS analysis); OS was tested at final analysis. Results: A total of 851 patients received induction treatment; 296 were randomized to pembrolizumab plus olaparib and 295 to pembrolizumab plus placebo. At interim analysis 2, with median follow-up of 27.1 months, median (95% confidence interval [CI]) PFS was 8.3 (6.7-9.7) months in the pembrolizumab plus olaparib group and 5.4 (4.1-5.6) months in the pembrolizumab plus placebo group (hazard ratio = 0.77, 95% CI: 0.63-0.93, p = 0.0040 [not significant at a one-sided superiority boundary of p = 0.003]). At final analysis, with median follow-up of 33.4 months, median (95% CI) OS was 19.1 (15.9-22.2) and 18.6 (16.0-21.6) months, respectively (hazard ratio = 1.01, 95% CI: 0.83-1.24, p = 0.5481). Treatment-related adverse events occurred in 76.5% and 65.1% of patients, respectively. Conclusions: Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo; neither PFS nor OS met the prespecified statistical significance boundary. No new safety signals were identified. Trial registration: ClinicalTrials.gov, NCT03976362. (c) 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and The Author(s). Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221370
url https://hdl.handle.net/2445/221370
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.jtho.2024.10.012
Journal of Thoracic Oncology, 2025, vol. 20, num. 2, p. 203-218
https://doi.org/10.1016/j.jtho.2024.10.012
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Hochmair et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Hochmair et al., 2024
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 16 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406056586674176
score 15,81155

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