Response of an HER2-Mutated NSCLC Patient to Trastuzumab Deruxtecan and Monitoring of Plasma ctDNA Levels by Liquid Biopsy

HER2-targeted therapy is currently the subject of several studies in lung cancer and other solid tumors using either tyrosine kinase inhibitors (TKI) or targeted-antibody–drug conjugates. We describe a 61-year-old female patient with HER2 mutated adenocarcinoma of the lungs who received chemo-immunotherapy, followed by trastuzumab deruxtecan (T-DXd) and third-line Ramucirumab/Docetaxel at disease progression. Plasma ctDNA monitoring was obtained at 12 timepoints during therapy and revealed HER2 mutation allele frequencies that corresponded to the clinical course of disease. HER2-targeted T-DXd therapy resulted in a profound clinical response and may be an option for NSCLC patients carrying an activated HER2 mutation. Longitudinal liquid biopsy quantification of the underlying driver alteration can serve as a powerful diagnostic tool to monitor course of therapy.