Optimizing early identification and management of trastuzumab deruxtecan-related interstitial lung disease: insights from a multidisciplinary expert panel

Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody-drug conjugate that has demonstrated substantial clinical efficacy across HER2-expressing malignancies. However, interstitial lung disease (ILD) represents a clinically relevant and potentially serious adverse event associated with its use, requiring early recognition, exclusion of alternative etiologies and coordinated multidisciplinary management. Delayed identification may increase the risk of severe pulmonary toxicity and premature discontinuation of an otherwise highly effective therapy. In this manuscript, we aim to provide practical guidance on the early detection and management of T-DXd-related ILD.

A structured multidisciplinary discussion involving oncologists, pneumologists, and radiologists was conducted to evaluate the epidemiology, risk factors, diagnostic pathways, and management strategies for ILD in patients treated with T-DXd. Evidence from the published literature was reviewed to inform and support the panel's recommendations.

ILD may arise in up to 15% of patients receiving T-DXd. While most events occur during the first year of treatment, continued vigilance is warranted throughout therapy. High-resolution computed tomography (HRCT) is essential for early detection, and prompt treatment interruption combined with timely corticosteroid therapy is critical to prevent progression. The panel emphasized the importance of standardized imaging protocols, structured radiologic reporting, early multidisciplinary involvement, and patient education to facilitate prompt recognition and management.

Proactive surveillance strategies, including baseline and interval HRCT, multidisciplinary collaboration and patient-centered monitoring, are essential to minimize ILD-related morbidity while preserving access to T-DXd therapy. The implementation of standardized clinical pathways and the development of biomarker-driven approaches may further improve personalized ILD risk management.