Trastuzumab Deruxtecan-Induced Myotoxicity: First Case Report About Myopathy in Patient With Normal Body Composition and Clinical Insights.

Trastuzumab deruxtecan (T-DXd) significantly improves outcomes in HER2-positive or low metastatic breast cancer (MBC), but systematic documentation of its myotoxicity is lacking. A 45-year-old woman with HER2-low MBC and normal body composition (BMI 22.9 kg/m, visceral adipose area [VAT] 69.1 cm) developed T-DXd myopathy. She experienced dysphagia, Grade III myalgia, and creatine kinase (CK) peak of 1755 U/L, with MRI confirming lumbar subcutaneous edema and paraspinal muscle swelling. T-DXd was discontinued. Supportive therapy included hydration, urine alkalization by sodium bicarbonate, glutathione, and magnesium isoglycyrrhizinate. By Day 8, CK decreased to 539 U/L with myalgia improvement. After 13 days off therapy, CK rebounded to 1735 U/L with Grade III myalgia, which resolved upon reinitiating support. This case report presents the first documented instance of severe T-DXd-related myopathy in a patient with normal body composition. The observed case outcomes suggest that the combination of glutathione and magnesium isoglycyrrhizinate could potentially reduce CK levels and alleviate T-DXd-associated muscle pain. However, the observed clinical efficacy is based on an individual case. Extrapolation of these clinical outcomes requires large-scale randomized controlled trials with rigorous covariate adjustment.

© 2025 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.