Characterization of the safety profile of trastuzumab deruxtecan by dose: a pooled analysis across DESTINY studies

作者：Yeon Hee Park, Javier Cortés, Shanu Modi, Sara A. Hurvitz, Giampaolo Bianchini, Hiroji Iwata, Kohei Shitara, Salvatore Siena, Yasushi Goto, Geoffrey Y. Ku, Charles A. Powell, Sandra M. Swain, Meena Arunachalam, Martin Janek, Yingkai Cheng, Changan Chu, Purnima Verma, Nataliya Kuptsova‐Clarkson, Elton Mathias, Erin Goodman, Hope S. Rugo · 发表于：The Oncologist · 年份：2025 · DOI：10.1093/oncolo/oyaf396 · 被引用次数：4 · 研究领域：HER2/EGFR in Cancer Research、Lung Cancer Research Studies、Colorectal Cancer Treatments and Studies

BACKGROUND: Trastuzumab deruxtecan (T-DXd), an approved human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, may cause treatment-emergent adverse events (TEAEs), most commonly gastrointestinal and hematologic TEAEs. This pooled analysis evaluated TEAEs across 2 doses of T-DXd in patients with different cancers to support safe and effective real-world use. PATIENTS AND METHODS: Data were pooled from 9 phase I-III clinical trials (DS8201-A-J101; DESTINY-Breast01/02/03/04; DESTINY-Lung01/02; DESTINY-Gastric01/02) of T-DXd 5.4 or 6.4 mg/kg every 3 weeks in patients (N = 1678) with metastatic breast, gastric, or lung cancer with varying HER2 expression or HER2 mutation status. Nausea, vomiting, neutropenia, fatigue, and interstitial lung disease (ILD) were evaluated for time to onset and dose-related outcomes. Antiemetic analysis was limited before a 2020 protocol change recommending prophylaxis. RESULTS: Common TEAEs (in ≥20%) were fatigue, nausea, vomiting, neutropenia, anemia, and thrombocytopenia; mostly grade 1 or 2. TEAEs leading to dose reduction, drug interruption, and discontinuation with T-DXd were 22.6%, 42.8%, and 17.7% (5.4 mg/kg), and 29.7%, 47.6%, and 16.6% (6.4 mg/kg), respectively. Neutropenia, nausea, and fatigue occurred in 34.6%, 74.6%, and 56.5% of patients (5.4 mg/kg) and 49.3%, 65.5%, and 52.8% (6.4 mg/kg). Adjudicated drug-related ILD occurred in 12.0% and 10.9%, respectively. CONCLUSION: Gastrointestinal and hematologic TEAEs w...