Abstract
A 67-year-old patient with metastatic lung adenocarcinoma harboring a HER2 V659E mutation received trastuzumab deruxtecan (T-DXd) as second-line treatment. The V659E mutation is a rare alteration located in the transmembrane domain of HER2. The antitumor effect observed in this patient was comparable to that reported in a previous phase 2 trial, in which most patients had mutations in the kinase domain. Here, we present the detailed clinical course and discuss the findings from a molecular biological perspective.