Recognizing and Treating Interstitial Lung Disease Associated With Trastuzumab Deruxtecan

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Interstitial lung disease (ILD) represents a unique and serious toxicity associated with trastuzumab deruxtecan, occurring in approximately 10% to 15% of patients receiving antibody-drug conjugate (ADC) therapy. Dr Preeshagul emphasizes the subtle, “cryptic” presentation of ILD, which may manifest as gradual shortness of breath or persistent dry cough that can be mistakenly attributed to GERD or reactive airway disease. Early recognition requires high clinical suspicion and careful monitoring of respiratory symptoms in patients receiving HER2-targeted ADCs.

The management approach for ADC-related ILD involves immediate drug discontinuation, comprehensive pulmonary evaluation, and prompt corticosteroid therapy. Unlike immunotherapy-related pneumonitis, ADC-induced ILD may be less steroid-responsive and require additional immunosuppressive agents typically used in rheumatologic conditions. Pulmonary function tests, imaging studies, and multidisciplinary collaboration with pulmonology specialists are essential components of ILD evaluation and management.

Treatment decisions for grade 2 ILD present clinical challenges requiring individualized patient discussions and careful risk-benefit analysis. While grade 3-4 ILD prohibits drug rechallenge, grade 2 cases may allow cautious retreatment at reduced doses with intensive monitoring if symptoms respond quickly to steroids. The decision depends on patient preferences, available alternative treatments, and the speed of symptom resolution. Proactive ILD screening and early intervention are crucial for preventing progression to severe, life-threatening respiratory complications.