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

IntroductionTrastuzumab 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.MethodsA 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.ResultsThirty-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.ConclusionILD risk with T-DXd differs by severity and data source. Vigilant monitoring is essential, particularly in heavily pretreated patients.