Systematic review and meta-analysis of risk of interstitial lung disease/pneumonitis with trastuzumab deruxtecan in patients with breast cancer brain metastases

Although trastuzumab deruxtecan (T-DXd) demonstrated intracranial efficacy in HER2-positive breast cancer brain metastases (BCBM), its association with interstitial lung disease (ILD)/pneumonitis is a critical safety concern in this high-risk population. Systematic review and meta-analysis by researchers from the Cancer Hospital of Dalian University of Technology and Liaoning Cancer Hospital & Institute (Shenyang, China) conducted a systematic review and meta-analysis of the risk of ILD/pneumonitis with use of T-DXd in BCBM patients. In the literature through July 2025, nine studies involving 684 BCBM patients were identified. The pooled incidence rates for all-grade and grade ≥ 3 ILD/pneumonitis were 10% (95% CI 5-16) and 2% (1-4), respectively, whereas no fatal ILD events were reported. ILD/pneumonitis led to discontinuation in 11% of patients. The authors conclude that, although no fatal ILD was observed, the high discontinuation rate underscores the imperative for vigilant monitoring of T-DXd-associated pulmonary toxicity in BCBM patients.