Real-world characteristics of trastuzumab deruxtecan-related interstitial lung disease in Japanese patients with breast cancer and gastric cancer

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Abstract
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.
Funding Information
  • Daiichi Sankyo Co., Ltd. In March 2019

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