Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial

Background: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we...

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Autores: Michels, Sebastian|||0000-0003-3164-870X, Massutí, Bartomeu|||0000-0002-7608-3952, Vasyliv, I., Stratmann, Jan Alexander, Frank, Julia, Adams, Anne, Felip, Enriqueta|||0000-0002-7620-0098, Grohé, Christian, Rodríguez-Abreu, Delvys|||0000-0003-0506-1366, Bischoff, Helger G., Carcereny, Enric|||0000-0001-5235-5602, Corral, Jesús M., Pereira, Eva, Fassunke, Jana, Fischer, Rieke Nila, Insa, Amelia|||0000-0002-3438-6170, Koleczko, Sophia, Nogova, Lucia|||0000-0002-4502-1812, Reck, Martin|||0000-0002-5348-4462, Reutter, Theresa, Riedel, Richard, Schaufler, Diana, Scheffler, Matthias|||0000-0002-9031-1368, Weisthoff, Mathilda|||0000-0001-6536-3898, Provencio Pulla, Mariano|||0000-0001-6315-7919, Merkelbach-Bruse, Sabine, Hellmich, Martin|||0000-0001-5174-928X, Sebastian, Martin|||0000-0002-0404-7741, Büttner, Reinhard H., Persigehl, Thorsten|||0000-0001-5928-4405, Rosell, Rafael|||0000-0003-0817-3400, Wolf, Jürgen
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311108
Acceso en línea:https://ddd.uab.cat/record/311108
https://dx.doi.org/urn:doi:10.1016/j.esmoop.2024.102237
Access Level:acceso abierto
Palabra clave:Lung cancer
ROS1
Crizotinib
Overall survival
EUCROSS
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spelling Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trialMichels, Sebastian|||0000-0003-3164-870XMassutí, Bartomeu|||0000-0002-7608-3952Vasyliv, I.Stratmann, Jan AlexanderFrank, JuliaAdams, AnneFelip, Enriqueta|||0000-0002-7620-0098Grohé, ChristianRodríguez-Abreu, Delvys|||0000-0003-0506-1366Bischoff, Helger G.Carcereny, Enric|||0000-0001-5235-5602Corral, Jesús M.Pereira, EvaFassunke, JanaFischer, Rieke NilaInsa, Amelia|||0000-0002-3438-6170Koleczko, SophiaNogova, Lucia|||0000-0002-4502-1812Reck, Martin|||0000-0002-5348-4462Reutter, TheresaRiedel, RichardSchaufler, DianaScheffler, Matthias|||0000-0002-9031-1368Weisthoff, Mathilda|||0000-0001-6536-3898Provencio Pulla, Mariano|||0000-0001-6315-7919Merkelbach-Bruse, SabineHellmich, Martin|||0000-0001-5174-928XSebastian, Martin|||0000-0002-0404-7741Büttner, Reinhard H.Persigehl, Thorsten|||0000-0001-5928-4405Rosell, Rafael|||0000-0003-0817-3400Wolf, JürgenLung cancerROS1CrizotinibOverall survivalEUCROSSBackground: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. Materials and methods: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. Results: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. Conclusions: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/311108https://dx.doi.org/urn:doi:10.1016/j.esmoop.2024.102237reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3111082026-06-06T12:50:31Z
dc.title.none.fl_str_mv Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
title Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
spellingShingle Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
Michels, Sebastian|||0000-0003-3164-870X
Lung cancer
ROS1
Crizotinib
Overall survival
EUCROSS
title_short Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
title_full Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
title_fullStr Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
title_full_unstemmed Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
title_sort Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
dc.creator.none.fl_str_mv Michels, Sebastian|||0000-0003-3164-870X
Massutí, Bartomeu|||0000-0002-7608-3952
Vasyliv, I.
Stratmann, Jan Alexander
Frank, Julia
Adams, Anne
Felip, Enriqueta|||0000-0002-7620-0098
Grohé, Christian
Rodríguez-Abreu, Delvys|||0000-0003-0506-1366
Bischoff, Helger G.
Carcereny, Enric|||0000-0001-5235-5602
Corral, Jesús M.
Pereira, Eva
Fassunke, Jana
Fischer, Rieke Nila
Insa, Amelia|||0000-0002-3438-6170
Koleczko, Sophia
Nogova, Lucia|||0000-0002-4502-1812
Reck, Martin|||0000-0002-5348-4462
Reutter, Theresa
Riedel, Richard
Schaufler, Diana
Scheffler, Matthias|||0000-0002-9031-1368
Weisthoff, Mathilda|||0000-0001-6536-3898
Provencio Pulla, Mariano|||0000-0001-6315-7919
Merkelbach-Bruse, Sabine
Hellmich, Martin|||0000-0001-5174-928X
Sebastian, Martin|||0000-0002-0404-7741
Büttner, Reinhard H.
Persigehl, Thorsten|||0000-0001-5928-4405
Rosell, Rafael|||0000-0003-0817-3400
Wolf, Jürgen
author Michels, Sebastian|||0000-0003-3164-870X
author_facet Michels, Sebastian|||0000-0003-3164-870X
Massutí, Bartomeu|||0000-0002-7608-3952
Vasyliv, I.
Stratmann, Jan Alexander
Frank, Julia
Adams, Anne
Felip, Enriqueta|||0000-0002-7620-0098
Grohé, Christian
Rodríguez-Abreu, Delvys|||0000-0003-0506-1366
Bischoff, Helger G.
Carcereny, Enric|||0000-0001-5235-5602
Corral, Jesús M.
Pereira, Eva
Fassunke, Jana
Fischer, Rieke Nila
Insa, Amelia|||0000-0002-3438-6170
Koleczko, Sophia
Nogova, Lucia|||0000-0002-4502-1812
Reck, Martin|||0000-0002-5348-4462
Reutter, Theresa
Riedel, Richard
Schaufler, Diana
Scheffler, Matthias|||0000-0002-9031-1368
Weisthoff, Mathilda|||0000-0001-6536-3898
Provencio Pulla, Mariano|||0000-0001-6315-7919
Merkelbach-Bruse, Sabine
Hellmich, Martin|||0000-0001-5174-928X
Sebastian, Martin|||0000-0002-0404-7741
Büttner, Reinhard H.
Persigehl, Thorsten|||0000-0001-5928-4405
Rosell, Rafael|||0000-0003-0817-3400
Wolf, Jürgen
author_role author
author2 Massutí, Bartomeu|||0000-0002-7608-3952
Vasyliv, I.
Stratmann, Jan Alexander
Frank, Julia
Adams, Anne
Felip, Enriqueta|||0000-0002-7620-0098
Grohé, Christian
Rodríguez-Abreu, Delvys|||0000-0003-0506-1366
Bischoff, Helger G.
Carcereny, Enric|||0000-0001-5235-5602
Corral, Jesús M.
Pereira, Eva
Fassunke, Jana
Fischer, Rieke Nila
Insa, Amelia|||0000-0002-3438-6170
Koleczko, Sophia
Nogova, Lucia|||0000-0002-4502-1812
Reck, Martin|||0000-0002-5348-4462
Reutter, Theresa
Riedel, Richard
Schaufler, Diana
Scheffler, Matthias|||0000-0002-9031-1368
Weisthoff, Mathilda|||0000-0001-6536-3898
Provencio Pulla, Mariano|||0000-0001-6315-7919
Merkelbach-Bruse, Sabine
Hellmich, Martin|||0000-0001-5174-928X
Sebastian, Martin|||0000-0002-0404-7741
Büttner, Reinhard H.
Persigehl, Thorsten|||0000-0001-5928-4405
Rosell, Rafael|||0000-0003-0817-3400
Wolf, Jürgen
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lung cancer
ROS1
Crizotinib
Overall survival
EUCROSS
topic Lung cancer
ROS1
Crizotinib
Overall survival
EUCROSS
description Background: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. Materials and methods: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. Results: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. Conclusions: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/311108
https://dx.doi.org/urn:doi:10.1016/j.esmoop.2024.102237
url https://ddd.uab.cat/record/311108
https://dx.doi.org/urn:doi:10.1016/j.esmoop.2024.102237
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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