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T-DXd Pneumonitis — SCE Medical Oncology MCQ

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ModerateImmunotherapy & Targeted TherapyT-DXd PneumonitisSCE Medical Oncology

A patient is receiving trastuzumab deruxtecan (T-DXd) for HER2-low metastatic breast cancer. She develops progressive dyspnoea and dry cough after 3 months of treatment. CT shows bilateral ground-glass opacities. What specific T-DXd toxicity must be managed urgently?

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Correct answer: A — Interstitial lung disease/pneumonitis — a potentially fatal toxicity of T-DXd requiring immediate drug discontinuation and corticosteroids

ILD/pneumonitis is the most clinically significant toxicity of T-DXd, occurring in approximately 10-15% of patients (grade 3+ in ~3%, with rare fatalities). It requires immediate T-DXd discontinuation (permanent for grade ≥2), infection exclusion and corticosteroid therapy. Risk appears higher with prior thoracic radiation, lung disease, and Japanese ethnicity. Regular monitoring with pulse oximetry and CT assessment at early signs is critical. T-DXd should not be rechallenged after grade ≥2 ILD.

Reference: BNF Trastuzumab deruxtecan; ESMO 2024 Breast Cancer Guidelines; DESTINY-Breast04 safety data