Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.

Drug approval for early-stage breast cancer (EBC) has been historically granted in the context of registration trials based on adequate outcomes such as disease-free survival and overall survival. Improvements in long-term outcomes have made it more difficult to demonstrate the clinical benefit of a...

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Autores: Gion, M, Perez-Garcia, JM, Llombart-Cussac, A, Sampayo-Cordero, M, Cortes, J, Malfettone, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p12658
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/12658
Access Level:acceso abierto
Palabra clave:breast cancer subtypes
early breast cancer
intermediate endpoints
neoadjuvant therapy
pathological complete response
surrogate markers
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spelling Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.Gion, MPerez-Garcia, JMLlombart-Cussac, ASampayo-Cordero, MCortes, JMalfettone, Abreast cancer subtypesearly breast cancerintermediate endpointsneoadjuvant therapypathological complete responsesurrogate markersDrug approval for early-stage breast cancer (EBC) has been historically granted in the context of registration trials based on adequate outcomes such as disease-free survival and overall survival. Improvements in long-term outcomes have made it more difficult to demonstrate the clinical benefit of a new cancer drug in large, randomized, comparative clinical trials. Therefore, the use of surrogate endpoints rather than traditional measures allows for cancer drug trials to proceed with smaller sample sizes and shorter follow-up periods, which reduces drug development time. Among surrogate endpoints for breast cancer, the increase in pathological complete response (pCR) rates was considered appropriate for accelerated drug approval. The association between pCR and long-term outcomes was strongest in patients with aggressive tumor subtypes, such as triple-negative and human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor-negative breast cancers. Whereas in hormone receptor-positive/HER2-negative EBC, the most accepted surrogate markers for endocrine therapy-based trials include changes in Ki67 and the preoperative endocrine prognostic index. Beyond the classic endpoints, further prognostic tools are required to provide EBC patients with individualized and effective therapies, and the neoadjuvant setting provides an excellent platform for drug development and biomarker discovery. Nowadays, the availability of multigene signatures is offering a standardized quantitative and reproducible tool to potentiate the efficacy of standard treatment for high-risk patients and develop de-escalated treatments for patients at lower risk of relapse. In this article, we first evaluate the surrogacies used for long-term outcomes and the underlying evidence supporting the use of each surrogate endpoint for the accelerated or regular drug approval process in EBC. Next, we provide an overview of the most recent studies and innovative strategies in a (neo)adjuvant setting as a platform to accelerate new drug approval. Finally, we highlight some clinical trials aimed at tailoring systemic treatment of EBC using prognosis-related factors or early biomarkers of drug sensitivity or resistance.SAGE PUBLICATIONS LTD2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/12658Therapeutic Advances in Medical OncologyISSN: 17588340ISSNe: 17588359reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p126582026-06-11T12:45:17Z
dc.title.none.fl_str_mv Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
title Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
spellingShingle Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
Gion, M
breast cancer subtypes
early breast cancer
intermediate endpoints
neoadjuvant therapy
pathological complete response
surrogate markers
title_short Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
title_full Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
title_fullStr Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
title_full_unstemmed Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
title_sort Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects.
dc.creator.none.fl_str_mv Gion, M
Perez-Garcia, JM
Llombart-Cussac, A
Sampayo-Cordero, M
Cortes, J
Malfettone, A
author Gion, M
author_facet Gion, M
Perez-Garcia, JM
Llombart-Cussac, A
Sampayo-Cordero, M
Cortes, J
Malfettone, A
author_role author
author2 Perez-Garcia, JM
Llombart-Cussac, A
Sampayo-Cordero, M
Cortes, J
Malfettone, A
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv breast cancer subtypes
early breast cancer
intermediate endpoints
neoadjuvant therapy
pathological complete response
surrogate markers
topic breast cancer subtypes
early breast cancer
intermediate endpoints
neoadjuvant therapy
pathological complete response
surrogate markers
description Drug approval for early-stage breast cancer (EBC) has been historically granted in the context of registration trials based on adequate outcomes such as disease-free survival and overall survival. Improvements in long-term outcomes have made it more difficult to demonstrate the clinical benefit of a new cancer drug in large, randomized, comparative clinical trials. Therefore, the use of surrogate endpoints rather than traditional measures allows for cancer drug trials to proceed with smaller sample sizes and shorter follow-up periods, which reduces drug development time. Among surrogate endpoints for breast cancer, the increase in pathological complete response (pCR) rates was considered appropriate for accelerated drug approval. The association between pCR and long-term outcomes was strongest in patients with aggressive tumor subtypes, such as triple-negative and human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor-negative breast cancers. Whereas in hormone receptor-positive/HER2-negative EBC, the most accepted surrogate markers for endocrine therapy-based trials include changes in Ki67 and the preoperative endocrine prognostic index. Beyond the classic endpoints, further prognostic tools are required to provide EBC patients with individualized and effective therapies, and the neoadjuvant setting provides an excellent platform for drug development and biomarker discovery. Nowadays, the availability of multigene signatures is offering a standardized quantitative and reproducible tool to potentiate the efficacy of standard treatment for high-risk patients and develop de-escalated treatments for patients at lower risk of relapse. In this article, we first evaluate the surrogacies used for long-term outcomes and the underlying evidence supporting the use of each surrogate endpoint for the accelerated or regular drug approval process in EBC. Next, we provide an overview of the most recent studies and innovative strategies in a (neo)adjuvant setting as a platform to accelerate new drug approval. Finally, we highlight some clinical trials aimed at tailoring systemic treatment of EBC using prognosis-related factors or early biomarkers of drug sensitivity or resistance.
publishDate 2021
dc.date.none.fl_str_mv 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://fisabio.portalinvestigacion.com/publicaciones/12658
url https://fisabio.portalinvestigacion.com/publicaciones/12658
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 SAGE PUBLICATIONS LTD
publisher.none.fl_str_mv SAGE PUBLICATIONS LTD
dc.source.none.fl_str_mv Therapeutic Advances in Medical Oncology
ISSN: 17588340
ISSNe: 17588359
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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