Real-world analysis of interstitial lung disease/pneumonitis in Japanese patients with breast cancer receiving trastuzumab deruxtecan

BACKGROUND: While trastuzumab deruxtecan (T-DXd) shows efficacy in various cancers, interstitial lung disease (ILD) and pneumonitis are significant risks associated with its use. Understanding these risks is crucial for effective management and safe administration of T-DXd. Therefore, we conducted a postmarketing surveillance study in Japan to investigate the incidence of ILD and related factors. METHODS: All patients with human epidermal growth factor receptor 2-positive unresectable or recurrent breast cancer who initiated T-DXd in Japan between May 25, 2020, and November 30, 2021, were included. The primary outcome was the incidence of adjudicated drug-related ILD, and its associated factors were investigated using a Cox proportional hazards model. RESULTS: The safety analysis set included 1,731 patients with a median (range) age of 60 (27–87) years. The median (range) duration of T-DXd treatment was 9.4 (0.7–17.9) months. A total of 24 (1.4%) and 11 (0.6%) patients had ILD as a medical history and comorbidity, respectively. The incidence of any Grade, Grade ≥ 3, and Grade 5 adjudicated drug-related ILD was 16.1%, 3.0%, and 1.0%, respectively. The median (range) time from the first T-DXd treatment to the first onset of ILD was 5.1 (0.5–17.3) months. Male sex, higher body mass index (≥ median [21.3 kg/m2]), history/comorbidity of ILD, and impaired renal function were identified as baseline factors potentially associated with an increased risk of drug-related ILD. CONCLUSIONS: The incidence of adjudicated drug-related ILD in the real-world setting was similar to that observed in clinical trials.