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Peer-reviewedCC BY 4.0Frontiers in Oncology

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

  • Luca Licata1
  • Camilla Lisanti2
  • Grazia Arpino3,4
  • Lorenzo Cereser5,6
  • Nicholas Landini7
  • Francesco Macagno8
  • Francesco Pantano9
  • Ida Paris10
  • Mirco Pistelli11
  • Paolo Tarsia12
  • Giampaolo Bianchini1,13
13 affiliations
  1. 1Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  2. 2Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  3. 3Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
  4. 4Sbarro Institute at Temple University Philadelphia, Philadelphia, PA, United States.
  5. 5Department of Medicine (DMED), Institute of Radiology, University of Udine, Udine, Italy.
  6. 6Institute of Radiology, University Hospital S. Maria della Misericordia, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Udine, Italy.
  7. 7Department of Radiological, Oncological and Pathological Sciences, Policlinico Umberto I Hospital, "Sapienza" Rome University, Rome, Italy.
  8. 8Unit of Pneumology, Department of Neurosciences, Sensory Organs and Thorax, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
  9. 9Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
  10. 10Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
  11. 11Department of Medical Oncology, Azienda Ospedaliera Universitaria delle Marche, Ancona, Italy.
  12. 12Head of the Respiratory Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  13. 13Vita-Salute San Raffaele University, Milan, Italy.
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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Cite

BibTeXRIS
BibTeX
@article{licata2026optimizing,
  title = {{Optimizing early identification and management of trastuzumab deruxtecan-related interstitial lung disease: insights from a multidisciplinary expert panel}},
  author = {Luca Licata and Camilla Lisanti and Grazia Arpino and Lorenzo Cereser and Nicholas Landini and Francesco Macagno and Francesco Pantano and Ida Paris and Mirco Pistelli and Paolo Tarsia and Giampaolo Bianchini},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1899114},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1899114/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Optimizing early identification and management of trastuzumab deruxtecan-related interstitial lung disease: insights from a multidisciplinary expert panel
AU  - Luca Licata
AU  - Camilla Lisanti
AU  - Grazia Arpino
AU  - Lorenzo Cereser
AU  - Nicholas Landini
AU  - Francesco Macagno
AU  - Francesco Pantano
AU  - Ida Paris
AU  - Mirco Pistelli
AU  - Paolo Tarsia
AU  - Giampaolo Bianchini
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1899114
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1899114/full
AB  - Purpose: 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.  Methods: 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.  Results: 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.  Conclusion: 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.
SN  - 2234-943X
ER  -