Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial

Introduction: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in E...

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Autores: Michels, S, Massuti, B, Schildhaus, HU, Franklin, J, Sebastian, M, Felip, E, Grohe, C, Rodriguez-Abreu, D, Abdulla, DSY, Bischoff, H, Brandts, C, Carcereny, E, Corral, J, Dingemans, AMC, Pereira, E, Fassunke, J, Fischer, RN, Gardizi, M, Heukamp, L, Insa, A, Kron, A, Menon, R, Persigehl, T, Reck, M, Riedel, R, Rothschild, SI, Scheel, AH, Scheffler, M, Schmalz, P, Smit, EF, Limburg, M, Provencio, M, Karachaliou, N, Merkelbach-Bruse, S, Hellmich, M, Nogova, L, Buttner, R, Rosell, R, Wolf, J
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p3813
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/3813
Access Level:acceso abierto
Palavra-chave:Lung cancer
Targeted treatment
ROS1
Crizotinib
TP53
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spelling Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical TrialMichels, SMassuti, BSchildhaus, HUFranklin, JSebastian, MFelip, EGrohe, CRodriguez-Abreu, DAbdulla, DSYBischoff, HBrandts, CCarcereny, ECorral, JDingemans, AMCPereira, EFassunke, JFischer, RNGardizi, MHeukamp, LInsa, AKron, AMenon, RPersigehl, TReck, MRiedel, RRothschild, SIScheel, AHScheffler, MSchmalz, PSmit, EFLimburg, MProvencio, MKarachaliou, NMerkelbach-Bruse, SHellmich, MNogova, LButtner, RRosell, RWolf, JLung cancerTargeted treatmentROS1CrizotinibTP53Introduction: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). Patients and Methods: The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier:NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. Results: Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). Conclusions: Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.ELSEVIER SCIENCE INC2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/3813Journal of Thoracic OncologyISSN: 15560864ISSNe: 15561380reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p38132026-06-07T16:35:31Z
dc.title.none.fl_str_mv Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
title Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
spellingShingle Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
Michels, S
Lung cancer
Targeted treatment
ROS1
Crizotinib
TP53
title_short Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
title_full Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
title_fullStr Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
title_full_unstemmed Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
title_sort Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
dc.creator.none.fl_str_mv Michels, S
Massuti, B
Schildhaus, HU
Franklin, J
Sebastian, M
Felip, E
Grohe, C
Rodriguez-Abreu, D
Abdulla, DSY
Bischoff, H
Brandts, C
Carcereny, E
Corral, J
Dingemans, AMC
Pereira, E
Fassunke, J
Fischer, RN
Gardizi, M
Heukamp, L
Insa, A
Kron, A
Menon, R
Persigehl, T
Reck, M
Riedel, R
Rothschild, SI
Scheel, AH
Scheffler, M
Schmalz, P
Smit, EF
Limburg, M
Provencio, M
Karachaliou, N
Merkelbach-Bruse, S
Hellmich, M
Nogova, L
Buttner, R
Rosell, R
Wolf, J
author Michels, S
author_facet Michels, S
Massuti, B
Schildhaus, HU
Franklin, J
Sebastian, M
Felip, E
Grohe, C
Rodriguez-Abreu, D
Abdulla, DSY
Bischoff, H
Brandts, C
Carcereny, E
Corral, J
Dingemans, AMC
Pereira, E
Fassunke, J
Fischer, RN
Gardizi, M
Heukamp, L
Insa, A
Kron, A
Menon, R
Persigehl, T
Reck, M
Riedel, R
Rothschild, SI
Scheel, AH
Scheffler, M
Schmalz, P
Smit, EF
Limburg, M
Provencio, M
Karachaliou, N
Merkelbach-Bruse, S
Hellmich, M
Nogova, L
Buttner, R
Rosell, R
Wolf, J
author_role author
author2 Massuti, B
Schildhaus, HU
Franklin, J
Sebastian, M
Felip, E
Grohe, C
Rodriguez-Abreu, D
Abdulla, DSY
Bischoff, H
Brandts, C
Carcereny, E
Corral, J
Dingemans, AMC
Pereira, E
Fassunke, J
Fischer, RN
Gardizi, M
Heukamp, L
Insa, A
Kron, A
Menon, R
Persigehl, T
Reck, M
Riedel, R
Rothschild, SI
Scheel, AH
Scheffler, M
Schmalz, P
Smit, EF
Limburg, M
Provencio, M
Karachaliou, N
Merkelbach-Bruse, S
Hellmich, M
Nogova, L
Buttner, R
Rosell, R
Wolf, J
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
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lung cancer
Targeted treatment
ROS1
Crizotinib
TP53
topic Lung cancer
Targeted treatment
ROS1
Crizotinib
TP53
description Introduction: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). Patients and Methods: The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier:NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. Results: Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). Conclusions: Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
publishDate 2019
dc.date.none.fl_str_mv 2019
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://incliva.portalinvestigacion.com/publicaciones/3813
url https://incliva.portalinvestigacion.com/publicaciones/3813
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER SCIENCE INC
publisher.none.fl_str_mv ELSEVIER SCIENCE INC
dc.source.none.fl_str_mv Journal of Thoracic Oncology
ISSN: 15560864
ISSNe: 15561380
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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