Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Department of Gynecology and Obstetrics
- Ludwig Maximilian University of Munich
- Hospital Universitario 12 de Octubre
- University of Liege
- University of Hamburg
- Tokai University
- IRCCS Istituto Europeo di Oncologia - Milano
- Medical University of Vienna
- University of Basel
- St Vincent's University Hospital
- University College Cork
- Royal North Shore Hospital
- Beata María Ana Hospital
- Hospital Ramon y Cajal
- University of Padua
- IRCCS Istituto Oncologico Veneto - Padova
- IRCCS Hospital San Raffaele - Milano
- Vita-Salute San Raffaele University
- KU Leuven
- AstraZeneca
- Dana-Farber Cancer Institute
- Duke University
- University of Edinburgh
- University of Lausanne
- Cantonal Hospital Luzern
- Ente Ospedaliero Cantonale (EOC)
- Sahlgrenska University Hospital
- Lund University
- Uppsala University
- Hospital de Basurto
- Hospital Universitario Marques de Valdecilla
- Hospital Universitario Virgen de las Nieves
- Hospital Clínico Universitario de Salamanca
- University of Santiago de Compostela
- Hospital Ruber Internacional
- Hospital Universitario Virgen del Rocio
- Hospital Universitario de la Princesa
- University Hospital of Bellvitge
- Hospital Clinic of Barcelona
- Saint Mary's Hospital
- Champalimaud Foundation
- University of Porto
- Centralny Szpital Kliniczny Wojskowej Akademii Medycznej z Poliklinika
- University Clinical Center Gdansk
- Opolskie Centrum Onkologii im. prof. T. Koszarowskiego
- Maria Sklodowska-Curie Institute of Oncology
- Krakow University Hospital
- University Hospital Carl Gustav Carus Dresden
Abstract
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.
Details
Original language | English |
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Article number | 967 |
Pages (from-to) | 3717-3727 |
Number of pages | 11 |
Journal | Nature medicine |
Volume | 30 |
Issue number | 12 |
Publication status | Published - Dec 2024 |
Peer-reviewed | Yes |
External IDs
PubMed | 39271844 |
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