Incidence and risk factors for pneumonitis due to trastuzumab Deruxtecan in metastatic breast cancer: a retrospective cohort study

作者：Maria Azhar, Felipe Soto-Lanza, Amber Su, Nerea González, Kevin Bernal Medina, J. Alejandro Madrigal, Cesar Chavez Duran, Carlos Ignacio Rodriguez Reyna, Colin Chan, Girish S. Shroff, Roland L. Bassett, Sarah Pasyar, David Zhang, Vickie R. Shannon, Mehmet Altan, Melissa P. Mitchell, Funda Meric‐Bernstam, Jason Mouabbi, Rashmi K. Murthy, Saadia A. Faiz, Lara Bashoura, Bora Lim, Ajay Sheshadri · 发表于：Breast Cancer Research · 年份：2025 · DOI：10.1186/s13058-025-02151-1 · 被引用次数：3 · 研究领域：HER2/EGFR in Cancer Research、Lung Cancer Treatments and Mutations、Colorectal Cancer Treatments and Studies

BACKGROUND: Fam-trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that targets human epidermal growth factor receptor 2 (HER2) and delivers a topoisomerase inhibitor payload. T-DXd has been effectively used to treat metastatic breast cancer but causes pneumonitis in 10–15% of cases. Risk factors associated with T-DXd pneumonitis are not well described. RESEARCH QUESTION: What are the major clinical risk factors for T-DXd pneumonitis? STUDY DESIGN AND METHODS: We conducted a retrospective study of women with metastatic breast cancer at our institution treated with T-DXd as standard of care between 2020 and 2024. We collected clinical data, including demographics, relevant review of symptoms, molecular subtypes, prior treatments, and pulmonary comorbidities, from the electronic health record. A thoracic radiologist reviewed pre-treatment scans for the presence of interstitial lung abnormalities (ILAs). Radiation exposure variables were obtained from an institutional database. Pulmonologists reviewed all cases for the development of pneumonitis. We used univariable and multivariable Cox proportional hazard models to measure the association of clinical variables with the development of pneumonitis. RESULTS: Pneumonitis was observed in 19/203 patients (9.4%). In univariable analyses, pre-treatment shortness of breath (hazard ratio [HR] 3.9, 95% confidence interval [CI] 1.3–11.7), greater number of prior treatments (HR 1.2 per line, 95% CI 1.0-1.4), triple-negative...