Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial

Bevacizumab; Durvalumab; Càncer de mama HER2 negatiu

Detalles Bibliográficos
Autores: Quintela-Fandino, Miguel, Holgado, Esther, Manso, Luis, Cortés Castan, Javier, Morales, Serafin, Bermejo, Begoña, Colomer, Ramon
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
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:11351/6299
Acceso en línea:https://hdl.handle.net/11351/6299
Access Level:acceso abierto
Palabra clave:Mama - Càncer
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada
id ES_ee94d0be35d1a24b98aaa70528101a8f
oai_identifier_str oai:scientiasalut.gencat.cat:11351/6299
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
title Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
spellingShingle Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
Quintela-Fandino, Miguel
Mama - Càncer
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada
title_short Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
title_full Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
title_fullStr Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
title_full_unstemmed Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
title_sort Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial
dc.creator.none.fl_str_mv Quintela-Fandino, Miguel
Holgado, Esther
Manso, Luis
Cortés Castan, Javier
Morales, Serafin
Bermejo, Begoña
Colomer, Ramon
author Quintela-Fandino, Miguel
author_facet Quintela-Fandino, Miguel
Holgado, Esther
Manso, Luis
Cortés Castan, Javier
Morales, Serafin
Bermejo, Begoña
Colomer, Ramon
author_role author
author2 Holgado, Esther
Manso, Luis
Cortés Castan, Javier
Morales, Serafin
Bermejo, Begoña
Colomer, Ramon
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Quintela-Fandino M] Breast Cancer Clinical Research Unit – Clinical Research Program, CNIO - Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain. Medical Oncology Department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. Medical Oncology Department, Hospital Universitario Quiron, Pozuelo de Alarcon, Spain. [Holgado E] Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain. [Manso L] Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. [Morales S] Medical Oncology Department, Hospital Universitari Arnau Vilanova, Lleida, Spain. [Bermejo B] Medical Oncology Department, Hospital Clínico Universitario, Valencia, Spain. INCLIVA, Valencia, Spain. CIBERONC, Instituto Carlos III, Madrid, Spain. [Colomer R] Breast Cancer Clinical Research Unit – Clinical Research Program, CNIO - Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain. Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain. Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. [Cortes J] ION Institute of Oncology, Quironsalud Group – Madrid & Barcelona, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Mama - Càncer
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada
topic Mama - Càncer
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada
description Bevacizumab; Durvalumab; Càncer de mama HER2 negatiu
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
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/11351/6299
url https://hdl.handle.net/11351/6299
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Breast Cancer Research;22
https://doi.org/10.1186/s13058-020-01362-y
info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00354
info:eu-repo/grantAgreement/ES/PE2013-2016/SAF2017-83732-R
info:eu-repo/grantAgreement/ES/PE2013-2016/PIE15%2F00068
info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F01865
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
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
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_ 1869423734034530304
spelling Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trialQuintela-Fandino, MiguelHolgado, EstherManso, LuisCortés Castan, JavierMorales, SerafinBermejo, BegoñaColomer, RamonMama - CàncerMedicaments antineoplàstics - Ús terapèuticDISEASES::Neoplasms::Neoplasms by Site::Breast NeoplasmsANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy ProtocolsENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mamaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinadaBevacizumab; Durvalumab; Càncer de mama HER2 negatiuBevacizumab; Durvalumab; Cáncer de mama HER2 negativoBevacizumab; Durvalumab; HER2-negative breast cancerBackground Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangiogenic bevacizumab after bevacizumab monotherapy for advanced HER2-negative breast cancer. Methods Patients had advanced HER2-negative disease that progressed while receiving single-agent bevacizumab maintenance as a part of a previous chemotherapy plus bevacizumab regimen. Treatment consisted of bi-weekly durvalumab plus bevacizumab (10 mg/kg each i.v.). Peripheral-blood mononuclear cells (PBMCs) were obtained before the first durvalumab dose and every 4 weeks and immunophenotyped by flow-cytometry. A fresh pre-durvalumab tumor biopsy was obtained; gene-expression studies and immunohistochemical staining to assess vascular normalization and characterize the immune infiltrate were conducted. Patients were classified as “non-progressors” if they had clinical benefit (SD/PR/CR) at 4 months. The co-primary endpoints were the changes in the percentage T cell subpopulations in PBMCs in progressors versus non-progressors, and PFS/OS time. Results Twenty-six patients were accrued. Median PFS and OS were 3.5 and 11 months; a trend for a longer OS was detected for the hormone-positive subset (19.8 versus 7.4 months in triple-negatives; P = 0.11). Clinical benefit rate at 2 and 4 months was 60% and 44%, respectively, without significant differences between hormone-positive and triple-negative (P = 0.73). Non-progressors’ tumors displayed vascular normalization features as a result of previous bevacizumab, compared with generally abnormal patterns observed in progressors. Non-progressors also showed increased T-effector and T-memory signatures and decreased TREG signatures in gene expression studies in baseline—post-bevacizumab—tumors compared with progressors. Notably, analysis of PBMC populations before durvalumab treatment was concordant with the findings in tumor samples and showed a decreased percentage of circulating TREGs in non-progressors. Conclusions This study reporting on sequential bevacizumab+durvalumab in breast cancer showed encouraging activity in a heavily pre-treated cohort. The correlative studies agree with the preclinical rationale supporting an immunopriming effect exerted by antiangiogenic treatment, probably by reducing TREGs cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting.MQF is a recipient of the following grants: AES - PI16/00354 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF) and B2017/BMD3733 (Immunothercan-CM) - Call for Coordinated Research Groups from Madrid Region - Madrid Regional Government - ERDF funds. SM is a recipient of the following grants: Spanish Ministerio de Economía y Competitividad (MINECO) (SAF2017-83732-R; AEI/FEDER, EU) and co-funded by Comunidad de Madrid (B2017/BMD3733; Immunothercan-CM). RC is a recipient RC is a recipient of the ISCIII grants PIE15/00068 and PI17/01865. The study was also funded by CRIS Contra el Cancer Foundation and Astra Zeneca Spain. Astra Zeneca Spain provided durvalumab.BMCInstitut Català de la Salut[Quintela-Fandino M] Breast Cancer Clinical Research Unit – Clinical Research Program, CNIO - Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain. Medical Oncology Department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. Medical Oncology Department, Hospital Universitario Quiron, Pozuelo de Alarcon, Spain. [Holgado E] Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain. [Manso L] Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. [Morales S] Medical Oncology Department, Hospital Universitari Arnau Vilanova, Lleida, Spain. [Bermejo B] Medical Oncology Department, Hospital Clínico Universitario, Valencia, Spain. INCLIVA, Valencia, Spain. CIBERONC, Instituto Carlos III, Madrid, Spain. [Colomer R] Breast Cancer Clinical Research Unit – Clinical Research Program, CNIO - Spanish National Cancer Research Center, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain. Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain. Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. [Cortes J] ION Institute of Oncology, Quironsalud Group – Madrid & Barcelona, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202120212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/6299Scientiareponame:Scientia. Dipòsit d'Informació Digital del Departament de Salutinstname:Departament de Salut de la Generalitat de Catalunya (DS)InglésBreast Cancer Research;22https://doi.org/10.1186/s13058-020-01362-yinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00354info:eu-repo/grantAgreement/ES/PE2013-2016/SAF2017-83732-Rinfo:eu-repo/grantAgreement/ES/PE2013-2016/PIE15%2F00068info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F01865Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:scientiasalut.gencat.cat:11351/62992026-06-12T09:38:37Z
score 15,812429

Similares en LA Referencia