Trastuzumab Deruxtecan for ERBB2 -Mutant Metastatic Non–Small Cell Lung Cancer With or Without Brain Metastases

作者：Pasi A. Jänne, David Planchard, Kōichi Goto, Egbert F. Smit, Adrianus J. de Langen, Yasushi Goto, Kiichiro Ninomiya, Toshio Kubo, M. Pérol, Enriqueta Felip, Hidetoshi Hayashi, Kazuhiko Nakagawa, Junichi Shimizu, Misako Nagasaka, Kaline Pereira, Ayumi Taguchi, Ahmed Ali, Maha Karnoub, Rie Yonemochi, David Leung, Bob T. Li · 发表于：JAMA Network Open · 年份：2025 · DOI：10.1001/jamanetworkopen.2025.43107 · 被引用次数：15 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Lung Cancer Research Studies

Importance: Brain metastases reduce overall survival rates of patients with non-small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])-mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC. Objective: To assess the clinical effectiveness and safety of T-DXd 5.4 mg/kg and 6.4 mg/kg doses in patients with previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases. Design, Setting, and Participants: This post hoc secondary analysis pooled patients from the DESTINY-Lung01 (data cutoff date: December 3, 2021) and DESTINY-Lung02 (data cutoff date: December 23, 2022) clinical trials by T-DXd dose (5.4 mg/kg and 6.4 mg/kg). DESTINY-Lung01 was a multicenter, open-label, 2-cohort, nonrandomized phase 2 study, while DESTINY-Lung02 was a dose-blinded, multicenter, 2-cohort, randomized phase 2 study. Participants had a previously treated ERBB2-mutant metastatic NSCLC with or without untreated or previously treated stable brain metastases at baseline. All statistical analyses were performed from April 2023 to October 2024. Intervention: Patients received a T-DXd dose of either 5.4 mg/kg or 6.4 mg/kg intravenously every 3 weeks. Main Outcome and Measure: Systemic and intracranial effectiveness by blinded independent central review us...