Trastuzumab Deruxtecan–Induced Interstitial Lung Disease: A Systematic Review and Meta-Analysis of Clinical Trials and Real-World Evidence


Güren A. K., DEMİRCAN N. C., SARI M., KÖSTEK O., BAYOĞLU İ. V.

Cancer Control, cilt.33, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 33
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1177/10732748261451083
  • Dergi Adı: Cancer Control
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals
  • Anahtar Kelimeler: clinical trials, interstitial lung disease, meta-analysis, real-world data, trastuzumab deruxtecan
  • Marmara Üniversitesi Adresli: Evet

Özet

Introduction: Trastuzumab deruxtecan (T-DXd)-induced interstitial lung disease/pneumonitis (ILD) represents a clinically significant and potentially fatal toxicity. Discrepancies exist regarding its reported frequency and severity between clinical trials (CTs) and real-world data (RWD). This meta-analysis aims to evaluate the incidence of T-DXd-related ILD and investigate its differences between CTs and RWD. Methods: A systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Databases were searched from their inception through January 2026. CTs and real-world studies reporting T-DXd-related ILD were included in the analysis. Pooled incidences for all-grade, grade ≥3, and fatal ILD were calculated using random-effects models. Subgroup analyses comparing CTs and RWD, and meta-regression analyses for relevant outcomes were performed. Results: Thirty-five studies (19 CTs, 16 RWD) including 6840 patients were analyzed. The pooled incidence was 8.8% for all-grade ILD, 1.6% for grade ≥3 ILD, and 0.26% for fatal ILD. RWD was independently associated with lower reported rates of all-grade and fatal ILD, while prior lines of therapy were the main predictor of grade ≥3 ILD. Conclusion: ILD risk with T-DXd differs by severity and data source. Vigilant monitoring is essential, particularly in heavily pretreated patients.