Yutaka Fujiwara, Katsunori Oikado, Tomohisa Baba, Masahiko Kusumoto, Shinichi Sasaki, Masahiro Endo, Terufumi Kato, Yasuyuki Kurihara, Yoshinobu Saito, Kunihiro Yagihashi, Masafumi Sata, Yoshinao Sato, Hirotsugu Kenmotsu, Taiki Fukuda, Teppei Yamaguchi, Saiko Isshiki, Hiroshi Wakui, Haruki Kobayashi, Satoshi Ikeda, Motoyasu Kato, Ou Yamaguchi, Toshimi Takano, Ken Kato, Yoshiharu Hiruma, Koji Hirata, Wataru Hashimoto, Kazuyoshi Kuwano
Most T-DXd-related ILD cases were mild/moderate and corticosteroid-responsive; DAD pattern was associated with higher mortality. These findings underscore the importance of vigilant monitoring, early recognition, and prompt corticosteroid treatment to mitigate fatal T-DXd-related ILD.
BACKGROUND: Interstitial lung disease (ILD)/pneumonitis is an important adverse drug reaction associated with trastuzumab deruxtecan (T-DXd). This report comprehensively characterized clinical and imaging features of T-DXd-related ILD, systematically evaluated by an independent ILD Adjudication Committee (AC), in Japanese patients with breast/gastric cancer from all-patient post-marketing surveillance studies.
PATIENTS AND METHODS: This post hoc analysis evaluated independent ILD AC-adjudicated T-DXd-related ILD cases. Demographics, clinical/radiological features, time to onset, treatment interventions, and outcomes (followed up to 12 months from onset) were analyzed.
RESULTS: Among 2801 T-DXd-treated patients (breast cancer: 1731; gastric cancer: 1070), 421 potential cases were reviewed: 381 were adjudicated as T-DXd-related ILD (breast cancer: 278; gastric cancer: 103). Median age was 65.0 years, 75.1% were female, and 28.3% had a smoking history. ILD occurred throughout observation (including fatal cases ≥12 months post-initiation) with no specific onset window. Time to onset did not differ across CTCAE grades. Organizing pneumonia was the predominant imaging pattern (67.7%), followed by hypersensitivity pneumonitis (14.2%) and diffuse alveolar damage (DAD, 12.6%). Most cases (78.2%) were worst CTCAE Grade 1-2. Grade 5 ILD occurred in 30 patients (7.9%), with DAD the most common pattern (26 patients). Overall recovery was 83.5%. Corticosteroids were used in 54.6% of cases, with 79.3% responding. High-dose corticosteroids and additional immunosuppressants were ineffective in seven DAD cases.
CONCLUSIONS: Most T-DXd-related ILD cases were mild/moderate and corticosteroid-responsive; DAD pattern was associated with higher mortality. These findings underscore the importance of vigilant monitoring, early recognition, and prompt corticosteroid treatment to mitigate fatal T-DXd-related ILD.