Real-world activity of trastuzumab deruxtecan in heavily pretreated HER2-expressing ovarian cancer: focusing on HER2-low responses and CCNE1 amplification

Background: Trastuzumab deruxtecan (T-DXd) is active in HER2-expressing solid tumours, but trials excluded HER2 immunohistochemistry (IHC) 1+ disease, and data in pretreated ovarian cancer are lacking. We evaluated real-world T-DXd activity and genomic correlates in pretreated ovarian cancer, predominantly high-grade serous (HGSOC). Methods: HER2 expression was assessed in an unselected ovarian cancer cohort (N=74). Fifteen patients receiving off-label T-DXd (14 HGSOC, 1 clear cell; IHC 1+ to 3+) had HER2 status centrally confirmed using gastric-type criteria. Activity was assessed by intra-patient growth modulation index (GMI; progression-free survival [PFS] on T-DXd divided by PFS on the p