TY - JOUR
T1 - Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases
T2 - a phase 3b/4 trial
AU - the DESTINY-Breast12 study group
AU - Harbeck, Nadia
AU - Ciruelos, Eva
AU - Jerusalem, Guy
AU - Müller, Volkmar
AU - Niikura, Naoki
AU - Viale, Giuseppe
AU - Bartsch, Rupert
AU - Kurzeder, Christian
AU - Higgins, Michaela J.
AU - Connolly, Roisin M.
AU - Baron-Hay, Sally
AU - Gión, María
AU - Guarneri, Valentina
AU - Bianchini, Giampaolo
AU - Wildiers, Hans
AU - Escrivá-de-Romaní, Santiago
AU - Prahladan, Manoj
AU - Bridge, Helen
AU - Kuptsova-Clarkson, Nataliya
AU - Scotto, Nana
AU - Verma, Sunil
AU - Lin, Nancy U.
AU - Anders, Carey
AU - Hall, Peter
AU - Zaman, Khalil
AU - Aebi, Stefan
AU - Rossi, Lorenzo
AU - Klint, Leif
AU - Killander, Fredrika
AU - Schiza, Aglaia
AU - del Prado, Purificación Martínez
AU - González, Carmen Hinojo
AU - Flores, Encarnación González
AU - Sanchez, César Rodríguez
AU - López, Rafael López
AU - Castán, Javier Cortés
AU - Borrego, Manuel Ruiz
AU - Marti, Maria Pilar Lopez
AU - Gregori, Joaquin Gavilá
AU - Manich, Cristina Saura
AU - Losada, María Jesús Vidal
AU - Sousa, Ana Rita
AU - Cardoso, Fatima
AU - Simões, Joana
AU - Duchnowska, Renata
AU - Jassem, Jacek
AU - Radecka, Barbara
AU - Nowecki, Zbigniew
AU - Wysocki, Piotr
AU - Sætersdal, Anna
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2+ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2–based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9–67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9–65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5–68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2+ mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761.
AB - Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2+ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2–based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9–67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9–65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5–68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2+ mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761.
UR - https://www.scopus.com/pages/publications/85204005128
U2 - 10.1038/s41591-024-03261-7
DO - 10.1038/s41591-024-03261-7
M3 - Article
C2 - 39271844
AN - SCOPUS:85204005128
SN - 1078-8956
VL - 30
SP - 3717
EP - 3727
JO - Nature Medicine
JF - Nature Medicine
IS - 12
M1 - 967
ER -
SDG 3 Good Health and Well-being