Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study

Endometrial cancer; Genomic instability; Olaparib

Detalles Bibliográficos
Autores: Poveda, Andres, Oaknin Benzaquen, Ana Mazaltob, Rubio, Maria Jesus, Guerra, Eva, Fariñas Madrid, Lorena, Rodriguez Freixinos, Victor, López-Reig, Raquel, Redondo Sanchez, Andres
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Departament de Salut de la Generalitat de Catalunya (DS)
Repositorio:Scientia. Dipòsit d'Informació Digital del Departament de Salut
OAI Identifier:oai:scientiasalut.gencat.cat:11351/7879
Acceso en línea:https://hdl.handle.net/11351/7879
Access Level:acceso abierto
Palabra clave:Càncer - Tractament
Avaluació de resultats (Assistència sanitària)
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
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oai_identifier_str oai:scientiasalut.gencat.cat:11351/7879
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
title Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
spellingShingle Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
Poveda, Andres
Càncer - Tractament
Avaluació de resultats (Assistència sanitària)
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
title_short Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
title_full Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
title_fullStr Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
title_full_unstemmed Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
title_sort Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
dc.creator.none.fl_str_mv Poveda, Andres
Oaknin Benzaquen, Ana Mazaltob
Rubio, Maria Jesus
Guerra, Eva
Fariñas Madrid, Lorena
Rodriguez Freixinos, Victor
López-Reig, Raquel
Redondo Sanchez, Andres
author Poveda, Andres
author_facet Poveda, Andres
Oaknin Benzaquen, Ana Mazaltob
Rubio, Maria Jesus
Guerra, Eva
Fariñas Madrid, Lorena
Rodriguez Freixinos, Victor
López-Reig, Raquel
Redondo Sanchez, Andres
author_role author
author2 Oaknin Benzaquen, Ana Mazaltob
Rubio, Maria Jesus
Guerra, Eva
Fariñas Madrid, Lorena
Rodriguez Freixinos, Victor
López-Reig, Raquel
Redondo Sanchez, Andres
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Poveda A] Oncogynecologic Department, Initia Oncology, Hospital Quironsalud, Valencia, Spain. [Lopez-Reig R] Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. IVO-CIPF Joint Research Unit of Cancer, Príncipe Felipe Research Center (CIPF), Valencia, Spain. [Oaknin A, Fariñas-Madrid L] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Redondo A] Medical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Universidad Autónoma de Madrid (UAM), Madrid, Spain. [Rubio MJ] Medical Oncology Department, Universitary Hospital Reina Sofia, Cordoba, Spain. [Guerra E] Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. [Rodriguez-Freixinos V] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Càncer - Tractament
Avaluació de resultats (Assistència sanitària)
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
topic Càncer - Tractament
Avaluació de resultats (Assistència sanitària)
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
description Endometrial cancer; Genomic instability; Olaparib
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
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/11351/7879
url https://hdl.handle.net/11351/7879
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cancers;14(4)
https://doi.org/10.3390/cancers14040915
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Scientia
reponame:Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname:Departament de Salut de la Generalitat de Catalunya (DS)
instname_str Departament de Salut de la Generalitat de Catalunya (DS)
reponame_str Scientia. Dipòsit d'Informació Digital del Departament de Salut
collection Scientia. Dipòsit d'Informació Digital del Departament de Salut
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869409616185524224
spelling Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational StudyPoveda, AndresOaknin Benzaquen, Ana MazaltobRubio, Maria JesusGuerra, EvaFariñas Madrid, LorenaRodriguez Freixinos, VictorLópez-Reig, RaquelRedondo Sanchez, AndresCàncer - TractamentAvaluació de resultats (Assistència sanitària)DISEASES::NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyENFERMEDADES::neoplasiasOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaEndometrial cancer; Genomic instability; OlaparibCáncer endometrial; Inestabilidad genómica; OlaparibCàncer d'endometri; Inestabilitat genòmica; OlaparibWe hypothesized that the combination of olaparib and lurbinectedin maximizes DNA damage, thus increasing its efficacy. The POLA phase 1 trial established the recommended phase 2 dose of lurbinectedin as being 1.5 mg (day 1) and that of olaparib as being 250 mg/12 h (days 1–5) for a 21-day cycle. In phase 2, we explore the efficacy of the combination in terms of clinical response and its correlation with mutations in the HRR genes and the genomic instability (GI) parameters. Results: A total of 73 patients with high-grade ovarian (n = 46), endometrial (n = 26), and triple-negative breast cancer (n = 1) were treated with lurbinectedin and olaparib. Most patients (62%) received ≥3 lines of prior therapy. The overall response rate (ORR) and disease control rate (DCR) were 9.6% and 72.6%, respectively. The median progression-free survival (PFS) was 4.54 months (95% CI 3.0–5.2). Twelve (16.4%) patients were considered long-term responders (LTR), with a median PFS of 13.3 months. No clinical benefit was observed for cases with HRR gene mutation. In ovarian LTRs, although a direct association with GI and a total loss of heterozygosity (LOH) events was observed, the association did not reach statistical significance (p = 0.055). Globally, the total number of LOHs might be associated with the ORR (p =0.074). The most common grade 3–4 toxicities were anemia and thrombocytopenia, in 6 (8.2%) and 3 (4.1%) patients, respectively. Conclusion: The POLA study provides evidence that the administration of lurbinectedin and olaparib is feasible and tolerable, with a DCR of 72.6%. Different GI parameters showed associations with better responses.This trial was sponsored by AstraZeneca and PharmaMar, including supply of the drugs used in this study.MDPIInstitut Català de la Salut[Poveda A] Oncogynecologic Department, Initia Oncology, Hospital Quironsalud, Valencia, Spain. [Lopez-Reig R] Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. IVO-CIPF Joint Research Unit of Cancer, Príncipe Felipe Research Center (CIPF), Valencia, Spain. [Oaknin A, Fariñas-Madrid L] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Redondo A] Medical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Universidad Autónoma de Madrid (UAM), Madrid, Spain. [Rubio MJ] Medical Oncology Department, Universitary Hospital Reina Sofia, Cordoba, Spain. [Guerra E] Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. [Rodriguez-Freixinos V] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, CanadaVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/7879Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésCancers;14(4)https://doi.org/10.3390/cancers14040915Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/78792026-06-12T09:38:37Z
score 15,811543

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