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Peer-reviewedCC BY-NC 4.0Cancer Medicine

Real‐World Progression Patterns and Potential Prognostic Factors for Trastuzumab Deruxtecan‐Related Interstitial Lung Disease in Japanese Patients With Breast or Gastric Cancer

  • Shinichi Sasaki1
  • Katsunori Oikado2
  • Tomohisa Baba3
  • Masahiko Kusumoto4
  • Yutaka Fujiwara5
  • Masahiro Endo6
  • Terufumi Kato7
  • Yasuyuki Kurihara8
  • Yoshinobu Saito9
  • Kunihiro Yagihashi10
  • Masafumi Sata11
  • Yoshinao Sato12
15 more authors
  • Hirotsugu Kenmotsu13
  • Taiki Fukuda14
  • Teppei Yamaguchi5
  • Saiko Isshiki15
  • Hiroshi Wakui16
  • Haruki Kobayashi13
  • Satoshi Ikeda17
  • Motoyasu Kato18
  • Ou Yamaguchi19
  • Toshimi Takano20
  • Ken Kato21
  • Akiko Takenaka22
  • Koji Hirata22
  • Wataru Hashimoto23
  • Kazuyoshi Kuwano24
24 affiliations
  1. 1Department of Respiratory Medicine Juntendo University Urayasu Hospital Chiba Japan
  2. 2Department of Diagnostic Radiology Toranomon Hospital Tokyo Japan
  3. 3Department of Respiratory Medicine Kanagawa Cardiovascular & Respiratory Center Yokohama Japan
  4. 4Midtown Clinic East Tokyo Japan
  5. 5Department of Thoracic Oncology Aichi Cancer Center Hospital Nagoya Japan
  6. 6Division of Diagnostic Radiology Shizuoka Cancer Center Shizuoka Japan
  7. 7Center for Clinical Research and Trials Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan
  8. 8Department of Radiology Kyorin University Hospital Tokyo Japan
  9. 9Department of Respiratory Medicine Nippon Medical School Musashi Kosugi Hospital Kawasaki Japan
  10. 10Department of Radiology St. Marianna University Yokohama Seibu Hospital Yokohama Japan
  11. 11Department of Internal Medicine Kyowa Chuo Hospital Ibaraki Japan
  12. 12Department of Diagnostic Imaging The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan
  13. 13Division of Thoracic Oncology Shizuoka Cancer Center Shizuoka Japan
  14. 14Department of Radiology The Jikei University School of Medicine Tokyo Japan
  15. 15Department of Radiology Niiza‐Shiki Central General Hospital Saitama Japan
  16. 16Division of Respiratory Diseases, Department of Internal Medicine The Jikei University School of Medicine Tokyo Japan
  17. 17Department of Thoracic Oncology Kansai Medical University Hospital Osaka Japan
  18. 18Department of Respiratory Medicine Juntendo University Graduate School of Medicine Tokyo Japan
  19. 19Department of Respiratory Medicine Saitama Medical University International Medical Center Saitama Japan
  20. 20Breast Medical Oncology Department The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan
  21. 21Department of Head and Neck, Esophageal Medical Oncology and Gastrointestinal Medical Oncology National Cancer Center Hospital Tokyo Japan
  22. 22Department of Medical Safety Daiichi Sankyo Co., Ltd. Tokyo Japan
  23. 23Department of Data Intelligence Daiichi Sankyo Co., Ltd. Tokyo Japan
  24. 24Department of Respiratory Medicine International University of Health and Welfare Tokyo Japan
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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 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.

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 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.

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

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Cite

BibTeXRIS
BibTeX
@article{sasaki2026realworld,
  title = {{Real‐World Progression Patterns and Potential Prognostic Factors for Trastuzumab Deruxtecan‐Related Interstitial Lung Disease in Japanese Patients With Breast or Gastric Cancer}},
  author = {Shinichi Sasaki and Katsunori Oikado and Tomohisa Baba and Masahiko Kusumoto and Yutaka Fujiwara and Masahiro Endo and Terufumi Kato and Yasuyuki Kurihara and Yoshinobu Saito and Kunihiro Yagihashi and Masafumi Sata and Yoshinao Sato and Hirotsugu Kenmotsu and Taiki Fukuda and Teppei Yamaguchi and Saiko Isshiki and Hiroshi Wakui and Haruki Kobayashi and Satoshi Ikeda and Motoyasu Kato and Ou Yamaguchi and Toshimi Takano and Ken Kato and Akiko Takenaka and Koji Hirata and Wataru Hashimoto and Kazuyoshi Kuwano},
  journal = {Cancer Medicine},
  year = {2026},
  month = nov,
  doi = {10.1002/cam4.72489},
  url = {https://doi.org/10.1002/cam4.72489},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Real‐World Progression Patterns and Potential Prognostic Factors for Trastuzumab Deruxtecan‐Related Interstitial Lung Disease in Japanese Patients With Breast or Gastric Cancer
AU  - Shinichi Sasaki
AU  - Katsunori Oikado
AU  - Tomohisa Baba
AU  - Masahiko Kusumoto
AU  - Yutaka Fujiwara
AU  - Masahiro Endo
AU  - Terufumi Kato
AU  - Yasuyuki Kurihara
AU  - Yoshinobu Saito
AU  - Kunihiro Yagihashi
AU  - Masafumi Sata
AU  - Yoshinao Sato
AU  - Hirotsugu Kenmotsu
AU  - Taiki Fukuda
AU  - Teppei Yamaguchi
AU  - Saiko Isshiki
AU  - Hiroshi Wakui
AU  - Haruki Kobayashi
AU  - Satoshi Ikeda
AU  - Motoyasu Kato
AU  - Ou Yamaguchi
AU  - Toshimi Takano
AU  - Ken Kato
AU  - Akiko Takenaka
AU  - Koji Hirata
AU  - Wataru Hashimoto
AU  - Kazuyoshi Kuwano
PY  - 2026
DA  - 2026/11/09
JO  - Cancer Medicine
DO  - 10.1002/cam4.72489
UR  - https://doi.org/10.1002/cam4.72489
AB  - 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 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.  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 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.  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
SN  - 2045-7634
ER  -