{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:56:06Z","timestamp":1793314566349,"version":"4.5.0"},"reference-count":14,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: Trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, has significantly advanced the management of HER2-expressing malignancies. However, interstitial lung disease (ILD) remains a clinically significant adverse effect. Despite increasing clinical use of T-DXd, real-world data on ILD incidence, characteristics, and outcomes\u2014particularly in Middle Eastern populations remain limited. Methods: This retrospective study analyzed medical records of patients who received trastuzumab deruxtecan (T-DXd) at a tertiary care hospital. Data collected included demographics, tumor characteristics, prior treatments, and interstitial lung disease (ILD)-related outcomes. ILD events were identified and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics were used to summarize baseline characteristics and ILD features. Univariate logistic regression was performed to assess potential risk factors associated with ILD development. Kaplan\u2013Meier survival analysis was used to evaluate time-to-event outcomes, including time to ILD onset and resolution. Results: Among 65 patients with advanced stage IV cancer (90.8% with breast cancer), 16 (24.6%) developed ILD following T-DXd therapy. The median time to ILD onset was 125.5 days. The most common presenting symptoms were dyspnea and cough (50%). A history of ground-glass opacities was associated with increased odds of ILD (OR 2.7; p = 0.236), though not statistically significant. Patients with Grade \u2265 3 ILD had significantly lower oxygen saturation levels compared to those with milder grades (88.3% vs. 97.7%, p = 0.049). Median time to clinical resolution was 297 days (95% CI: 77.5\u2013516). No significant associations were observed with smoking history, pulmonary metastases, or prior thoracic radiation. Conclusions: In this real-world cohort, ILD occurred in nearly one-quarter of patients receiving T-DXd, predominantly within the first six months of treatment. The findings highlight the importance of early respiratory symptom monitoring and pulse oximetry\u2014particularly in patients with pre-existing pulmonary abnormalities. These results underscore the need for vigilant ILD surveillance strategies and further prospective studies to validate predictive risk factors and optimize management protocols.<\/jats:p>","DOI":"10.3390\/curroncol32100575","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T07:33:50Z","timestamp":1760686430000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Trastuzumab Deruxtecan-Associated Interstitial Lung Disease: Real-World Insights from a Tertiary Care Center"],"prefix":"10.3390","volume":"32","author":[{"given":"Ahmed S.","family":"Alanazi","sequence":"first","affiliation":[{"name":"Pharmacy Service Administration, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3611-0529","authenticated-orcid":false,"given":"Ahmed A.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0754-7493","authenticated-orcid":false,"given":"Abdalrhman","family":"Alanizi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Care Service, King Abdullah Bin Abdulaziz University Hospital, Riyadh 11564, Saudi Arabia"},{"name":"College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranad","family":"Babalghaith","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2324-1565","authenticated-orcid":false,"given":"Reema","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-5437","authenticated-orcid":false,"given":"Mohammed","family":"Alnuhait","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, Al-Dawadmi 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatoon","family":"Bakhribah","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1056\/NEJMoa1914510","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer","volume":"382","author":"Modi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1056\/NEJMoa2115022","article-title":"Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer","volume":"386","author":"Kim","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mercogliano, M.F., Bruni, S., Mauro, F.L., and Schillaci, R. (2023). Emerging Targeted Therapies for HER2-Positive Breast Cancer. Cancers, 15.","DOI":"10.3390\/cancers15071987"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100554","DOI":"10.1016\/j.esmoop.2022.100554","article-title":"Pooled analysis of drug-related interstitial lung disease and\/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies","volume":"7","author":"Powell","year":"2022","journal-title":"ESMO Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1111\/resp.14848","article-title":"Contemporary Concise Review 2023: Interstitial lung disease","volume":"29","author":"Moodley","year":"2024","journal-title":"Respirology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104274","DOI":"10.1016\/j.critrevonc.2024.104274","article-title":"Lung toxicity induced by anti-HER2 antibody\u2014Drug conjugates for breast cancer","volume":"195","author":"Chai","year":"2024","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa2112431","article-title":"Trastuzumab Deruxtecan in HER2-Mutant Non\u2013Small-Cell Lung Cancer","volume":"386","author":"Li","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1200\/OP.23.00097","article-title":"Detecting and Managing T-DXd\u2013Related Interstitial Lung Disease: The Five \u201cS\u201d Rules","volume":"19","author":"Tarantino","year":"2023","journal-title":"JCO Oncol. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1200\/JCO.2024.42.16_suppl.1024","article-title":"Real world experience of trastuzumab deruxtecan for the treatment of metastatic breast cancer in the UK","volume":"42","author":"Cheng","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s40265-022-01736-w","article-title":"Trastuzumab Deruxtecan-Induced Interstitial Lung Disease\/Pneumonitis in ERBB2-Positive Advanced Solid Malignancies: A Systematic Review","volume":"82","author":"Abuhelwa","year":"2022","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1200\/OP.22.00480","article-title":"Real-World Perspectives and Practices for Pneumonitis\/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2\u2013Expressing Metastatic Breast Cancer","volume":"19","author":"Rugo","year":"2023","journal-title":"JCO Oncol. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s40264-023-01328-x","article-title":"Clinical Guidance on the Monitoring and Management of Trastuzumab Deruxtecan (T-DXd)-Related Adverse Events: Insights from an Asia-Pacific Multidisciplinary Panel","volume":"46","author":"Chiu","year":"2023","journal-title":"Drug Saf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8019","DOI":"10.3390\/curroncol30090582","article-title":"Managing the Risk of Lung Toxicity with Trastuzumab Deruxtecan (T-DXd): A Canadian Perspective","volume":"30","author":"Henning","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1200\/JCO.2025.43.16_suppl.1015","article-title":"Treatment rechallenge after trastuzumab-deruxtecan\u2013related interstitial lung disease: A multi-institution cohort study","volume":"43","author":"Natsuhara","year":"2025","journal-title":"J. Clin. Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/10\/575\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T08:26:58Z","timestamp":1760689618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/10\/575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":14,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["curroncol32100575"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32100575","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}