TY - JOUR
T1 - Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression
T2 - the phase 2 DAISY trial
AU - Mosele, Fernanda
AU - Deluche, Elise
AU - Lusque, Amelie
AU - Le Bescond, Loïc
AU - Filleron, Thomas
AU - Pradat, Yoann
AU - Ducoulombier, Agnes
AU - Pistilli, Barbara
AU - Bachelot, Thomas
AU - Viret, Frederic
AU - Levy, Christelle
AU - Signolle, Nicolas
AU - Alfaro, Alexia
AU - Tran, Diep T.N.
AU - Garberis, Ingrid Judith
AU - Talbot, Hugues
AU - Christodoulidis, Stergios
AU - Vakalopoulou, Maria
AU - Droin, Nathalie
AU - Stourm, Aurelie
AU - Kobayashi, Maki
AU - Kakegawa, Tomoya
AU - Lacroix, Ludovic
AU - Saulnier, Patrick
AU - Job, Bastien
AU - Deloger, Marc
AU - Jimenez, Marta
AU - Mahier, Celine
AU - Baris, Vianney
AU - Laplante, Pierre
AU - Kannouche, Patricia
AU - Marty, Virginie
AU - Lacroix-Triki, Magali
AU - Diéras, Veronique
AU - André, Fabrice
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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 .)
AB - 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 .)
UR - http://www.scopus.com/inward/record.url?scp=85165446864&partnerID=8YFLogxK
U2 - 10.1038/s41591-023-02478-2
DO - 10.1038/s41591-023-02478-2
M3 - Article
AN - SCOPUS:85165446864
SN - 1078-8956
VL - 29
SP - 2110
EP - 2120
JO - Nature Medicine
JF - Nature Medicine
IS - 8
ER -