Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
- Creators
- 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
- 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
- Others:
- Institut Gustave Roussy (IGR)
- Hôpital Dupuytren [CHU Limoges]
- Institut Claudius Regaud
- Centre de vision numérique (CVN) ; Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay
- OPtimisation Imagerie et Santé (OPIS) ; Inria Saclay - Ile de France ; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de vision numérique (CVN) ; Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-CentraleSupélec-Université Paris-Saclay
- Mathématiques et Informatique pour la Complexité et les Systèmes (MICS) ; CentraleSupélec-Université Paris-Saclay
- Pôle de Chirurgie Oncologique générale, Gynécologique et Mammaire [Centre Antoine-Lacassagne] ; Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)
- Centre Léon Bérard [Lyon]
- Institut Paoli-Calmettes (IPC) ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
- Radiothérapie [Centre François Baclesse] ; Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC) ; Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
- Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa) ; Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
- Daiichi Sankyo Inc. ; Daiichi Sankyo Co.
- UNICANCER
- Université Paris-Saclay
- Intégrité du génome et cancers (IGC) ; École Pratique des Hautes Études (EPHE) ; Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
- Centre Eugène Marquis (CRLCC)
- AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
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 .)
Abstract
International audience
Additional details
- URL
- https://hal.science/hal-04265717
- URN
- urn:oai:HAL:hal-04265717v1
- Origin repository
- UNICA