{ "abstract": "Background: Interstitial lung disease (ILD)/pneumonitis is a safety concern with trastuzumab deruxtecan (T‐DXd). We characterized post‐onset changes in ILD severity and imaging patterns, and explored potential prognostic factors for fatal T‐DXd‐related ILD in Japanese patients with breast or gastric cancer.\n\nMethods: This post hoc analysis included 381 independently adjudicated T‐DXd‐related ILD cases from two Japanese all‐patient post‐marketing surveillance studies. We described transitions from onset to worst Common Terminology Criteria for Adverse Events grade and imaging pattern changes. Exploratory tumor type‐stratified Cox proportional hazards models were used to assess factors associated with time to fatal (Grade 5) ILD. The variable with the highest hazard ratio (HR) and each of the remaining significant univariate factors (p < 0.05 or a 95% confidence interval excluding 1) meeting the criteria were included in two‐covariate multivariable models.\n\nResults: At ILD onset, 60.1% of patients had Grade 1 ILD. Overall, 30 of the 381 adjudicated ILD cases (7.9%) progressed to fatal Grade 5, initially presenting with Grade 1 (n = 9), 2 (n = 5), or 3 (n = 16); time to death was 3–173 days. Of 24 cases with imaging pattern changes, 14 transitioned from nondiffuse alveolar damage (non‐DAD) to DAD (10 were fatal). Abnormal C‐reactive protein (CRP) at onset had the highest HR in univariate analyses. In separate CRP‐adjusted two‐covariate multivariable models, preexisting ILD and several onset factors (dyspnea; abnormal SpO2/lactate dehydrogenase/Krebs von den Lungen‐6; pleural/cardiac effusion; DAD pattern; traction bronchiectasis) were associated with fatal ILD. An organizing pneumonia pattern was associated with a lower hazard.\n\nConclusions: T‐DXd‐related ILD may progress rapidly to fatal outcomes, even from low‐grade or non‐DAD presentations, and several onset factors (e.g., elevated CRP, decreased SpO2, and DAD pattern) were associated with fatal ILD outcomes. These findings are exploratory and should not be used to determine whether to initiate or withhold corticosteroids. Guideline‐concordant ILD management remains essential regardless of these factors, while their potential role in identifying patients requiring closer monitoring warrants further validation.\n\nTrial Registration: The breast cancer and the gastric cancer surveys were registered at the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/en‐top) under the identifiers jRCT1080225197 and jRCT2001200001, respectively", "abstract_shown": true, "affiliations": [ "Department of Respiratory Medicine Juntendo University Urayasu Hospital Chiba Japan", "Department of Diagnostic Radiology Toranomon Hospital Tokyo Japan", "Department of Respiratory Medicine Kanagawa Cardiovascular & Respiratory Center Yokohama Japan", "Midtown Clinic East Tokyo Japan", "Department of Thoracic Oncology Aichi Cancer Center Hospital Nagoya Japan", "Division of Diagnostic Radiology Shizuoka Cancer Center Shizuoka Japan", "Center for Clinical Research and Trials Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan", "Department of Radiology Kyorin University Hospital Tokyo Japan", "Department of Respiratory Medicine Nippon Medical School Musashi Kosugi Hospital Kawasaki Japan", "Department of Radiology St. Marianna University Yokohama Seibu Hospital Yokohama Japan", "Department of Internal Medicine Kyowa Chuo Hospital Ibaraki Japan", "Department of Diagnostic Imaging The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan", "Division of Thoracic Oncology Shizuoka Cancer Center Shizuoka Japan", "Department of Radiology The Jikei University School of Medicine Tokyo Japan", "Department of Radiology Niiza‐Shiki Central General Hospital Saitama Japan", "Division of Respiratory Diseases, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan", "Department of Thoracic Oncology Kansai Medical University Hospital Osaka Japan", "Department of Respiratory Medicine Juntendo University Graduate School of Medicine Tokyo Japan", "Department of Respiratory Medicine Saitama Medical University International Medical Center Saitama Japan", "Breast Medical Oncology Department The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan", "Department of Head and Neck, Esophageal Medical Oncology and Gastrointestinal Medical Oncology National Cancer Center Hospital Tokyo Japan", "Department of Medical Safety Daiichi Sankyo Co., Ltd. Tokyo Japan", "Department of Data Intelligence Daiichi Sankyo Co., Ltd. Tokyo Japan", "Department of Respiratory Medicine International University of Health and Welfare Tokyo Japan" ], "article_type": "research article", "arxiv": null, "author_total": 27, "authors": [ { "affs": [ 0 ], "name": "Shinichi Sasaki", "orcid": "0000-0002-2257-7658" }, { "affs": [ 1 ], "name": "Katsunori Oikado" }, { "affs": [ 2 ], "name": "Tomohisa Baba", "orcid": "0000-0003-4294-634X" }, { "affs": [ 3 ], "name": "Masahiko Kusumoto", "orcid": "0000-0002-4557-3609" }, { "affs": [ 4 ], "name": "Yutaka Fujiwara", "orcid": "0000-0001-6981-0800" }, { "affs": [ 5 ], "name": "Masahiro Endo", "orcid": "0000-0002-2484-5839" }, { "affs": [ 6 ], "name": "Terufumi Kato", "orcid": "0000-0002-5853-1424" }, { "affs": [ 7 ], "name": "Yasuyuki Kurihara" }, { "affs": [ 8 ], "name": "Yoshinobu Saito" }, { "affs": [ 9 ], "name": "Kunihiro Yagihashi" }, { "affs": [ 10 ], "name": "Masafumi Sata", "orcid": "0000-0002-5414-6510" }, { "affs": [ 11 ], "name": "Yoshinao Sato", "orcid": "0000-0003-1313-5089" }, { "affs": [ 12 ], "name": "Hirotsugu Kenmotsu", "orcid": "0000-0003-0590-9259" }, { "affs": [ 13 ], "name": "Taiki Fukuda", "orcid": "0000-0001-9173-738X" }, { "affs": [ 4 ], "name": "Teppei Yamaguchi", "orcid": "0000-0002-8909-5709" }, { "affs": [ 14 ], "name": "Saiko Isshiki" }, { "affs": [ 15 ], "name": "Hiroshi Wakui", "orcid": "0000-0002-3729-1716" }, { "affs": [ 12 ], "name": "Haruki Kobayashi", "orcid": "0000-0002-3386-8063" }, { "affs": [ 16 ], "name": "Satoshi Ikeda", "orcid": "0000-0001-5203-7911" }, { "affs": [ 17 ], "name": "Motoyasu Kato", "orcid": "0000-0002-3217-5118" }, { "affs": [ 18 ], "name": "Ou Yamaguchi" }, { "affs": [ 19 ], "name": "Toshimi Takano", "orcid": "0000-0002-8417-5291" }, { "affs": [ 20 ], "name": "Ken Kato", "orcid": "0000-0002-1733-5072" }, { "affs": [ 21 ], "name": "Akiko Takenaka", "orcid": "0009-0009-2926-4687" }, { "affs": [ 21 ], "name": "Koji Hirata", "orcid": "0000-0002-6633-9934" }, { "affs": [ 22 ], "name": "Wataru Hashimoto", "orcid": "0009-0007-3682-502X" }, { "affs": [ 23 ], "name": "Kazuyoshi Kuwano" } ], "bibtex": "https://research.draconitic.com/paper/5s7ep1dj85ben.bib", "cited_by": 0, "doi": "10.1002/cam4.72489", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13748707/", "id": "5s7ep1dj85ben", "issns": [ "2045-7634" ], "landing_url": "https://doi.org/10.1002/cam4.72489", "language": "en", "licence": "CC-BY-NC-4.0", "licence_label": "CC BY-NC 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research Article" ], [ "openalex", "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis" ] ], "openalex": "W7225745075", "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cam4.72489", "pmcid": "PMC13748707", "pmid": "43004521", "published": "2026-11-09", "publisher": "Wiley", "ris": "https://research.draconitic.com/paper/5s7ep1dj85ben.ris", "sources": [ { "first_seen": "2026-11-13T12:26:39Z", "native_id": "PMC13748707", "source": "pmc", "url": "https://doi.org/10.1002/cam4.72489" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis", "subfield": "general" } ], "title": "Real‐World Progression Patterns and Potential Prognostic Factors for Trastuzumab Deruxtecan‐Related Interstitial Lung Disease in Japanese Patients With Breast or Gastric Cancer", "title_text": "Real‐World Progression Patterns and Potential Prognostic Factors for Trastuzumab Deruxtecan‐Related Interstitial Lung Disease in Japanese Patients With Breast or Gastric Cancer", "type": "peer-reviewed", "updated_at": "2026-11-13T12:26:39Z", "url": "https://research.draconitic.com/paper/5s7ep1dj85ben", "venue": "Cancer Medicine", "versions": [] }