Real‐World Progression Patterns and Potential Prognostic Factors for Trastuzumab Deruxtecan‐Related Interstitial Lung Disease in Japanese Patients With Breast or Gastric Cancer
Year: 2026
Type: article
Abstract: 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. Methods 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. Results 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 SpO 2 /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. Conclusions 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 SpO 2 , 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. Trial 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
Source: Cancer Medicine
DOI: 10.1002/cam4.72489
Authors: Shinichi Sasaki, Katsunori Oikado, Tomohisa Baba, Masahiko Kusumoto, Yutaka Fujiwara, Masahiro Endo, Terufumi Kato, Yasuyuki Kurihara, Yoshinobu Saito, Kunihiro Yagihashi, Masafumi Sata, Yoshinao Sato, Hirotsugu Kenmotsu, Taiki Fukuda, Teppei Yamaguchi, Saiko Isshiki, Hiroshi Wakui, Haruki Kobayashi, Satoshi Ikeda, Motoyasu Kato, Ou Yamaguchi, Toshimi Takano, Ken Kato, Akiko Takenaka, Koji Hirata, Wataru Hashimoto, Kazuyoshi Kuwano
Institutions: Juntendo University Urayasu Hospital, Toranomon Hospital, Kanagawa Cardiovascular and Respiratory Center, Aichi Cancer Center, Aichi Cancer Center Hospital, Shizuoka Cancer Center, Tokyo Metropolitan Komagome Hospital, Kyorin University Hospital, Nippon Medical School Musashi Kosugi Hospital, Yokohama City Seibu Hospital, The Cancer Institute Hospital, Japanese Foundation For Cancer Research, Jikei University School of Medicine, NIIZASHIKI Central General Hospital, Kansai Medical University Hospital, Juntendo University, Saitama International Medical Center, Saitama Medical University, National Cancer Center Hospital, Daiichi-Sankyo (Japan), International University of Health and Welfare
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,700
Funder: Daiichi Sankyo Company
OpenAlex ID: W7225745075