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 principales:	María Gion, José Manuel Pérez-García, Antonio Llombart-Cussac, Miguel Sampayo-Cordero, Javier Cortés, Andrea Malfettone
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8b548ce9bba54c9ca2cb0709f0aef8b1
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spelling	oai:doaj.org-article:8b548ce9bba54c9ca2cb0709f0aef8b12021-12-01T23:33:58ZSurrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects1758-835910.1177/17588359211059587https://doaj.org/article/8b548ce9bba54c9ca2cb0709f0aef8b12021-11-01T00:00:00Zhttps://doi.org/10.1177/17588359211059587https://doaj.org/toc/1758-8359Drug 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.María GionJosé Manuel Pérez-GarcíaAntonio Llombart-CussacMiguel Sampayo-CorderoJavier CortésAndrea MalfettoneSAGE PublishingarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENTherapeutic Advances in Medical Oncology, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 María Gion José Manuel Pérez-García Antonio Llombart-Cussac Miguel Sampayo-Cordero Javier Cortés Andrea Malfettone Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects
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.
format	article
author	María Gion José Manuel Pérez-García Antonio Llombart-Cussac Miguel Sampayo-Cordero Javier Cortés Andrea Malfettone
author_facet	María Gion José Manuel Pérez-García Antonio Llombart-Cussac Miguel Sampayo-Cordero Javier Cortés Andrea Malfettone
author_sort	María Gion
title	Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects
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
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/8b548ce9bba54c9ca2cb0709f0aef8b1
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Surrogate endpoints for early-stage breast cancer: a review of the state of the art, controversies, and future prospects

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