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Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial

The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2...

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Autores principales: Mosele, Fernanda, Deluche, Elise, Lusque, Amelie, Le Bescond, Loïc, Filleron, Thomas, Pradat, Yoann, Ducoulombier, Agnes, Pistilli, Barbara, Bachelot, Thomas, Viret, Frederic, Levy, Christelle, Signolle, Nicolas, Alfaro, Alexia, Tran, Diep T. N., Garberis, Ingrid Judith, Talbot, Hugues, Christodoulidis, Stergios, Vakalopoulou, Maria, Droin, Nathalie, Stourm, Aurelie, Kobayashi, Maki, Kakegawa, Tomoya, Lacroix, Ludovic, Saulnier, Patrick, Job, Bastien, Deloger, Marc, Jimenez, Marta, Mahier, Celine, Baris, Vianney, Laplante, Pierre, Kannouche, Patricia, Marty, Virginie, Lacroix-Triki, Magali, Diéras, Veronique, André, Fabrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427426/
https://www.ncbi.nlm.nih.gov/pubmed/37488289
http://dx.doi.org/10.1038/s41591-023-02478-2
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author Mosele, Fernanda
Deluche, Elise
Lusque, Amelie
Le Bescond, Loïc
Filleron, Thomas
Pradat, Yoann
Ducoulombier, Agnes
Pistilli, Barbara
Bachelot, Thomas
Viret, Frederic
Levy, Christelle
Signolle, Nicolas
Alfaro, Alexia
Tran, Diep T. N.
Garberis, Ingrid Judith
Talbot, Hugues
Christodoulidis, Stergios
Vakalopoulou, Maria
Droin, Nathalie
Stourm, Aurelie
Kobayashi, Maki
Kakegawa, Tomoya
Lacroix, Ludovic
Saulnier, Patrick
Job, Bastien
Deloger, Marc
Jimenez, Marta
Mahier, Celine
Baris, Vianney
Laplante, Pierre
Kannouche, Patricia
Marty, Virginie
Lacroix-Triki, Magali
Diéras, Veronique
André, Fabrice
author_facet Mosele, Fernanda
Deluche, Elise
Lusque, Amelie
Le Bescond, Loïc
Filleron, Thomas
Pradat, Yoann
Ducoulombier, Agnes
Pistilli, Barbara
Bachelot, Thomas
Viret, Frederic
Levy, Christelle
Signolle, Nicolas
Alfaro, Alexia
Tran, Diep T. N.
Garberis, Ingrid Judith
Talbot, Hugues
Christodoulidis, Stergios
Vakalopoulou, Maria
Droin, Nathalie
Stourm, Aurelie
Kobayashi, Maki
Kakegawa, Tomoya
Lacroix, Ludovic
Saulnier, Patrick
Job, Bastien
Deloger, Marc
Jimenez, Marta
Mahier, Celine
Baris, Vianney
Laplante, Pierre
Kannouche, Patricia
Marty, Virginie
Lacroix-Triki, Magali
Diéras, Veronique
André, Fabrice
author_sort Mosele, Fernanda
collection PubMed
description The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3–81) in cohort 1, 37.5% (95% CI 26.4–49.7) in cohort 2 and 29.7% (95% CI 15.9–47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8–64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7–65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960.)
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spelling pubmed-104274262023-08-17 Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial Mosele, Fernanda Deluche, Elise Lusque, Amelie Le Bescond, Loïc Filleron, Thomas Pradat, Yoann Ducoulombier, Agnes Pistilli, Barbara Bachelot, Thomas Viret, Frederic Levy, Christelle Signolle, Nicolas Alfaro, Alexia Tran, Diep T. N. Garberis, Ingrid Judith Talbot, Hugues Christodoulidis, Stergios Vakalopoulou, Maria Droin, Nathalie Stourm, Aurelie Kobayashi, Maki Kakegawa, Tomoya Lacroix, Ludovic Saulnier, Patrick Job, Bastien Deloger, Marc Jimenez, Marta Mahier, Celine Baris, Vianney Laplante, Pierre Kannouche, Patricia Marty, Virginie Lacroix-Triki, Magali Diéras, Veronique André, Fabrice Nat Med Article The mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3–81) in cohort 1, 37.5% (95% CI 26.4–49.7) in cohort 2 and 29.7% (95% CI 15.9–47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8–64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7–65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960.) Nature Publishing Group US 2023-07-24 2023 /pmc/articles/PMC10427426/ /pubmed/37488289 http://dx.doi.org/10.1038/s41591-023-02478-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Mosele, Fernanda
Deluche, Elise
Lusque, Amelie
Le Bescond, Loïc
Filleron, Thomas
Pradat, Yoann
Ducoulombier, Agnes
Pistilli, Barbara
Bachelot, Thomas
Viret, Frederic
Levy, Christelle
Signolle, Nicolas
Alfaro, Alexia
Tran, Diep T. N.
Garberis, Ingrid Judith
Talbot, Hugues
Christodoulidis, Stergios
Vakalopoulou, Maria
Droin, Nathalie
Stourm, Aurelie
Kobayashi, Maki
Kakegawa, Tomoya
Lacroix, Ludovic
Saulnier, Patrick
Job, Bastien
Deloger, Marc
Jimenez, Marta
Mahier, Celine
Baris, Vianney
Laplante, Pierre
Kannouche, Patricia
Marty, Virginie
Lacroix-Triki, Magali
Diéras, Veronique
André, Fabrice
Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
title Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
title_full Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
title_fullStr Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
title_full_unstemmed Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
title_short Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
title_sort trastuzumab deruxtecan in metastatic breast cancer with variable her2 expression: the phase 2 daisy trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427426/
https://www.ncbi.nlm.nih.gov/pubmed/37488289
http://dx.doi.org/10.1038/s41591-023-02478-2
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