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Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial

Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can en...

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Autores principales: Buisseret, Laurence, Loirat, Delphine, Aftimos, Philippe, Maurer, Christian, Punie, Kevin, Debien, Véronique, Kristanto, Paulus, Eiger, Daniel, Goncalves, Anthony, Ghiringhelli, François, Taylor, Donatienne, Clatot, Florent, Van den Mooter, Tom, Ferrero, Jean-Marc, Bonnefoi, Hervé, Canon, Jean-Luc, Duhoux, Francois P., Mansi, Laura, Poncin, Renaud, Barthélémy, Philippe, Isambert, Nicolas, Denis, Zoë, Catteau, Xavier, Salgado, Roberto, Agostinetto, Elisa, de Azambuja, Evandro, Rothé, Françoise, Craciun, Ligia, Venet, David, Romano, Emanuela, Stagg, John, Paesmans, Marianne, Larsimont, Denis, Sotiriou, Christos, Ignatiadis, Michail, Piccart-Gebhart, Martine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622534/
https://www.ncbi.nlm.nih.gov/pubmed/37919269
http://dx.doi.org/10.1038/s41467-023-42744-y
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author Buisseret, Laurence
Loirat, Delphine
Aftimos, Philippe
Maurer, Christian
Punie, Kevin
Debien, Véronique
Kristanto, Paulus
Eiger, Daniel
Goncalves, Anthony
Ghiringhelli, François
Taylor, Donatienne
Clatot, Florent
Van den Mooter, Tom
Ferrero, Jean-Marc
Bonnefoi, Hervé
Canon, Jean-Luc
Duhoux, Francois P.
Mansi, Laura
Poncin, Renaud
Barthélémy, Philippe
Isambert, Nicolas
Denis, Zoë
Catteau, Xavier
Salgado, Roberto
Agostinetto, Elisa
de Azambuja, Evandro
Rothé, Françoise
Craciun, Ligia
Venet, David
Romano, Emanuela
Stagg, John
Paesmans, Marianne
Larsimont, Denis
Sotiriou, Christos
Ignatiadis, Michail
Piccart-Gebhart, Martine
author_facet Buisseret, Laurence
Loirat, Delphine
Aftimos, Philippe
Maurer, Christian
Punie, Kevin
Debien, Véronique
Kristanto, Paulus
Eiger, Daniel
Goncalves, Anthony
Ghiringhelli, François
Taylor, Donatienne
Clatot, Florent
Van den Mooter, Tom
Ferrero, Jean-Marc
Bonnefoi, Hervé
Canon, Jean-Luc
Duhoux, Francois P.
Mansi, Laura
Poncin, Renaud
Barthélémy, Philippe
Isambert, Nicolas
Denis, Zoë
Catteau, Xavier
Salgado, Roberto
Agostinetto, Elisa
de Azambuja, Evandro
Rothé, Françoise
Craciun, Ligia
Venet, David
Romano, Emanuela
Stagg, John
Paesmans, Marianne
Larsimont, Denis
Sotiriou, Christos
Ignatiadis, Michail
Piccart-Gebhart, Martine
author_sort Buisseret, Laurence
collection PubMed
description Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.
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spelling pubmed-106225342023-11-04 Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial Buisseret, Laurence Loirat, Delphine Aftimos, Philippe Maurer, Christian Punie, Kevin Debien, Véronique Kristanto, Paulus Eiger, Daniel Goncalves, Anthony Ghiringhelli, François Taylor, Donatienne Clatot, Florent Van den Mooter, Tom Ferrero, Jean-Marc Bonnefoi, Hervé Canon, Jean-Luc Duhoux, Francois P. Mansi, Laura Poncin, Renaud Barthélémy, Philippe Isambert, Nicolas Denis, Zoë Catteau, Xavier Salgado, Roberto Agostinetto, Elisa de Azambuja, Evandro Rothé, Françoise Craciun, Ligia Venet, David Romano, Emanuela Stagg, John Paesmans, Marianne Larsimont, Denis Sotiriou, Christos Ignatiadis, Michail Piccart-Gebhart, Martine Nat Commun Article Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms. Nature Publishing Group UK 2023-11-02 /pmc/articles/PMC10622534/ /pubmed/37919269 http://dx.doi.org/10.1038/s41467-023-42744-y 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
Buisseret, Laurence
Loirat, Delphine
Aftimos, Philippe
Maurer, Christian
Punie, Kevin
Debien, Véronique
Kristanto, Paulus
Eiger, Daniel
Goncalves, Anthony
Ghiringhelli, François
Taylor, Donatienne
Clatot, Florent
Van den Mooter, Tom
Ferrero, Jean-Marc
Bonnefoi, Hervé
Canon, Jean-Luc
Duhoux, Francois P.
Mansi, Laura
Poncin, Renaud
Barthélémy, Philippe
Isambert, Nicolas
Denis, Zoë
Catteau, Xavier
Salgado, Roberto
Agostinetto, Elisa
de Azambuja, Evandro
Rothé, Françoise
Craciun, Ligia
Venet, David
Romano, Emanuela
Stagg, John
Paesmans, Marianne
Larsimont, Denis
Sotiriou, Christos
Ignatiadis, Michail
Piccart-Gebhart, Martine
Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
title Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
title_full Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
title_fullStr Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
title_full_unstemmed Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
title_short Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
title_sort paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized synergy phase i/ii trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622534/
https://www.ncbi.nlm.nih.gov/pubmed/37919269
http://dx.doi.org/10.1038/s41467-023-42744-y
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