Dr Lynam on the Efficacy of Trastuzumab Detruxtecan in HER2-Expressing Ovarian Cancer

“The analysis of the use of trastuzumab deruxtecan in an ovarian cancer population is [based on] a phase 2 study that looked at patients who had varying levels of HER2 expression for solid tumor malignancies.”

Sarah Lynam, MD, an assistant professor in the Division of Gynecologic Oncology in the Department of Reproductive Biology at Case Western Reserve University School of Medicine, and an attending physician in the Division of Gynecologic Oncology at the Seidman Cancer Center at the University Hospitals Cleveland Medical Center, detailed the efficacy data of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the phase 2 DESTINY-PanTumor02 trial (NCT04482309).

The phase 2 analysis that evaluated trastuzumab deruxtecan across multiple solid tumor malignancies demonstrated an overall response rate of 45.0% (95% CI, 29.3%-61.5%) among patients with ovarian cancer treated with the agent, Lynam began. Of note, in the ovarian cohort, the median number of prior lines of treatment was 3, and 35.0% of patients had received 5 or more lines of therapy. In the study, the median overall survival was 13.2 months in all patients with ovarian cancer and 20.0 months in those with a HER2 expression of immunohistochemistry (IHC) 3+. These findings were considered particularly meaningful given that the study population included patients with varying levels of HER2 expression, she noted. Response rates appeared to be higher in patients with the greatest degree of HER2 expression, particularly those classified as HER2 IHC 3+, in which patients also demonstrated a significant duration of therapy response in the trial, she explained. However, these findings remain exploratory, as prospective validation in larger cohorts is still needed, she stated. Multiple phase 3 trials are now ongoing to further assess trastuzumab deruxtecan in epithelial ovarian cancers and to determine its role in the broader treatment landscape.

Furthermore, factors such as HER2 receptor affinity dimerization could influence treatment sensitivity, which emphasizes the complexity of HER2 biology in ovarian cancer and the need to refine biomarker strategies, Lynam asserted. As these studies mature, better characterization of HER2-driven disease may enable more precise patient selection and optimize the use of trastuzumab deruxtecan in a larger patient population with ovarian cancer, she concluded.