Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study

Breast cancer; Lurbinectedin; Response rate

Detalles Bibliográficos
Autores: Braña Garcia, Irene, Shapiro, G. I., Trigo, José Manuel, Boni, Valentina, Moreno, Victor, Pistilli, Barbara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
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:11351/8428
Acceso en línea:https://hdl.handle.net/11351/8428
Access Level:acceso abierto
Palabra clave:Mama - Càncer - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
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oai_identifier_str oai:recercat.cat:11351/8428
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
title Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
spellingShingle Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
Braña Garcia, Irene
Mama - Càncer - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
title_short Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
title_full Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
title_fullStr Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
title_full_unstemmed Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
title_sort Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study
dc.creator.none.fl_str_mv Braña Garcia, Irene
Shapiro, G. I.
Trigo, José Manuel
Boni, Valentina
Moreno, Victor
Pistilli, Barbara
author Braña Garcia, Irene
author_facet Braña Garcia, Irene
Shapiro, G. I.
Trigo, José Manuel
Boni, Valentina
Moreno, Victor
Pistilli, Barbara
author_role author
author2 Shapiro, G. I.
Trigo, José Manuel
Boni, Valentina
Moreno, Victor
Pistilli, Barbara
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Boni V] START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. [Pistilli B] Gustave Roussy, Villejuif, France. [Braña I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Shapiro GI] Dana-Farber Cancer Institute, Boston, USA. [Trigo J] Hospital Universitario Virgen De La Victoria, IBIMA, Málaga, Spain. [Moreno V] START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Mama - Càncer - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
topic Mama - Càncer - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
description Breast cancer; Lurbinectedin; Response rate
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/11351/8428
url https://hdl.handle.net/11351/8428
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv ESMO Open;7(5)
https://doi.org/10.1016/j.esmoop.2022.100571
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
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Scientia
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_ 1869412998245777408
spelling Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket studyBraña Garcia, IreneShapiro, G. I.Trigo, José ManuelBoni, ValentinaMoreno, VictorPistilli, BarbaraMama - Càncer - TractamentMedicaments antineoplàstics - Ús terapèuticDISEASES::Neoplasms::Neoplasms by Site::Breast NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsOther subheadings::Other subheadings::/therapeutic useENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mamaOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicosOtros calificadores::Otros calificadores::/uso terapéuticoBreast cancer; Lurbinectedin; Response rateCáncer de mama; Lurbinectedina; Tasa de respuestaCàncer de mama; Lurbinectedina; Taxa de respostaBackground Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. Patients and methods This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). Conclusions This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.This work was supported by PharmaMar S.A, including partial funding by grants from the Centro para el Desarrollo Tecnológico IndustrialCentro para el Desarrollo Tecnológico Industrial (CDTI) during the conduct of the study (grant number IDI-20150006). VS is supported by NIH [grant number R01CA242845]. MD Anderson Cancer Center Department of Investigational Cancer Therapeutics is supported by the Cancer Prevention and Research Institute of Texas [grant number RP1100584], the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy [grant number 1U01 CA180964], NCATS [grant number UL1 TR000371] (Center for Clinical and Translational Sciences) and the MD Anderson Cancer Center Support [grant number P30 CA016672].ElsevierInstitut Català de la Salut[Boni V] START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. [Pistilli B] Gustave Roussy, Villejuif, France. [Braña I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Shapiro GI] Dana-Farber Cancer Institute, Boston, USA. [Trigo J] Hospital Universitario Virgen De La Victoria, IBIMA, Málaga, Spain. [Moreno V] START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, SpainVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/8428Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésESMO Open;7(5)https://doi.org/10.1016/j.esmoop.2022.100571Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/84282026-05-29T05:05:01Z
score 15,812429

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