Final Analysis Results and Patient-Reported Outcomes From DESTINY-Lung02—A Dose-Blinded, Randomized, Phase 2 Study of Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic NSCLC

作者：Pasi A. Jänne, Yasushi Goto, Toshio Kubo, Kiichiro Ninomiya, Sang‐We Kim, David Planchard, Myung‐Ju Ahn, Egbert F. Smit, Adrianus J. de Langen, M. Pérol, Elvire Pons‐Tostivint, Silvia Novello, Hidetoshi Hayashi, Junichi Shimizu, Dong‐Wan Kim, Kaline Pereira, Fu-Chih Cheng, Ayumi Taguchi, Yingkai Cheng, K. Dunton, Ahmed Ali, Kōichi Goto · 发表于：Journal of Thoracic Oncology · 年份：2025 · DOI：10.1016/j.jtho.2025.07.129 · 被引用次数：26 · 研究领域：HER2/EGFR in Cancer Research、Lung Cancer Treatments and Mutations、Advanced Breast Cancer Therapies

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated HER2 (ERBB2) mutant (HER2m) metastatic NSCLC (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes. METHODS: DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary end point was confirmed objective response rate by blinded independent central review. RESULTS: As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 (8.2-20.7) months and 16.5 (9.4-20.8) months, respectively. Confirmed objective response rate (95% confidence interval) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%), respectively. Safety profile was acceptable and generally manageable. Accordingly, median treatment duration (Q1-Q3) was 7.7 (3.7-14.4) months and 8.3 (2.8-13.1) months; drug-related grade 3 or higher treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1 or 2 with one...