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Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Hormone receptor-positive (HR+)/HER2-negative is the most frequent subgroup of metastatic breast cancer (MBC). Important therapeutic advances in the treatment of this tumor type have been observed in the last 20 years, with the approval of numerous endocrine therapies (ET) with or wi...

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Autores principales: Schettini, Francesco, Giuliano, Mario, Giudici, Fabiola, Conte, Benedetta, De Placido, Pietro, Venturini, Sergio, Rognoni, Carla, Di Leo, Angelo, Locci, Mariavittoria, Jerusalem, Guy, Del Mastro, Lucia, Puglisi, Fabio, Conte, PierFranco, De Laurentiis, Michelino, Pusztai, Lajos, Rimawi, Mothaffar F., Schiff, Rachel, Arpino, Grazia, De Placido, Sabino, Prat, Aleix, Generali, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004645/
https://www.ncbi.nlm.nih.gov/pubmed/33810205
http://dx.doi.org/10.3390/cancers13061458
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author Schettini, Francesco
Giuliano, Mario
Giudici, Fabiola
Conte, Benedetta
De Placido, Pietro
Venturini, Sergio
Rognoni, Carla
Di Leo, Angelo
Locci, Mariavittoria
Jerusalem, Guy
Del Mastro, Lucia
Puglisi, Fabio
Conte, PierFranco
De Laurentiis, Michelino
Pusztai, Lajos
Rimawi, Mothaffar F.
Schiff, Rachel
Arpino, Grazia
De Placido, Sabino
Prat, Aleix
Generali, Daniele
author_facet Schettini, Francesco
Giuliano, Mario
Giudici, Fabiola
Conte, Benedetta
De Placido, Pietro
Venturini, Sergio
Rognoni, Carla
Di Leo, Angelo
Locci, Mariavittoria
Jerusalem, Guy
Del Mastro, Lucia
Puglisi, Fabio
Conte, PierFranco
De Laurentiis, Michelino
Pusztai, Lajos
Rimawi, Mothaffar F.
Schiff, Rachel
Arpino, Grazia
De Placido, Sabino
Prat, Aleix
Generali, Daniele
author_sort Schettini, Francesco
collection PubMed
description SIMPLE SUMMARY: Hormone receptor-positive (HR+)/HER2-negative is the most frequent subgroup of metastatic breast cancer (MBC). Important therapeutic advances in the treatment of this tumor type have been observed in the last 20 years, with the approval of numerous endocrine therapies (ET) with or without target therapies (TT). To improve our current knowledge and support clinical decision-making, we conducted a systematic literature and meta-analysis focused on the most relevant/promising first-/second-line ET ± TT of the last 20 years. We observed that CDK4/6-inhibitors(i) + ET were the most effective regimens. At the same time, mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant patients. Single agent ET might still be a valuable upfront treatment in endocrine sensitive and non-visceral disease. ABSTRACT: A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) ± target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making.
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spelling pubmed-80046452021-03-29 Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis Schettini, Francesco Giuliano, Mario Giudici, Fabiola Conte, Benedetta De Placido, Pietro Venturini, Sergio Rognoni, Carla Di Leo, Angelo Locci, Mariavittoria Jerusalem, Guy Del Mastro, Lucia Puglisi, Fabio Conte, PierFranco De Laurentiis, Michelino Pusztai, Lajos Rimawi, Mothaffar F. Schiff, Rachel Arpino, Grazia De Placido, Sabino Prat, Aleix Generali, Daniele Cancers (Basel) Systematic Review SIMPLE SUMMARY: Hormone receptor-positive (HR+)/HER2-negative is the most frequent subgroup of metastatic breast cancer (MBC). Important therapeutic advances in the treatment of this tumor type have been observed in the last 20 years, with the approval of numerous endocrine therapies (ET) with or without target therapies (TT). To improve our current knowledge and support clinical decision-making, we conducted a systematic literature and meta-analysis focused on the most relevant/promising first-/second-line ET ± TT of the last 20 years. We observed that CDK4/6-inhibitors(i) + ET were the most effective regimens. At the same time, mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant patients. Single agent ET might still be a valuable upfront treatment in endocrine sensitive and non-visceral disease. ABSTRACT: A precise assessment of the efficacy of first-/second-line endocrine therapies (ET) ± target therapies (TT) in clinically-relevant subgroups of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision-making, we thus conducted a systematic literature search to identify all first-/second-line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta-analysis to assess progression-free (PFS) and/or overall survival (OS) benefit in several clinically-relevant prespecified subgroups. Thirty-five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single-agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6-inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi-based combinations proved to be a valid therapeutic option in endocrine-resistant tumors, as well as PI3Ki + ET in PIK3CA-mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision-making. MDPI 2021-03-22 /pmc/articles/PMC8004645/ /pubmed/33810205 http://dx.doi.org/10.3390/cancers13061458 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Systematic Review
Schettini, Francesco
Giuliano, Mario
Giudici, Fabiola
Conte, Benedetta
De Placido, Pietro
Venturini, Sergio
Rognoni, Carla
Di Leo, Angelo
Locci, Mariavittoria
Jerusalem, Guy
Del Mastro, Lucia
Puglisi, Fabio
Conte, PierFranco
De Laurentiis, Michelino
Pusztai, Lajos
Rimawi, Mothaffar F.
Schiff, Rachel
Arpino, Grazia
De Placido, Sabino
Prat, Aleix
Generali, Daniele
Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
title Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
title_full Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
title_fullStr Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
title_full_unstemmed Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
title_short Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis
title_sort endocrine-based treatments in clinically-relevant subgroups of hormone receptor-positive/her2-negative metastatic breast cancer: systematic review and meta-analysis
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004645/
https://www.ncbi.nlm.nih.gov/pubmed/33810205
http://dx.doi.org/10.3390/cancers13061458
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