HER2-directed therapy with Trastuzumab deruxtecan in recurrent mucinous ovarian carcinoma: complete clinical response and response to rechallenge.

Background: Mucinous ovarian carcinoma (MOC) is a rare and relatively chemo resistant subtype of epithelial ovarian cancer for which limited evidence-based guidelines exist. Human Epidermal growth factor Receptor 2 (HER2) overexpression occurs in up to 35% of MOC cases; however, targeted therapies are often used off-label because of the paucity of disease-specific clinical trial data. Fam-trastuzumab- deruxtecan-nxki (T-DXd), an antibody-drug conjugate approved for HER2-positive solid tumors, has not been well studied in MOC. Case report: A 37-year-old woman with recurrent, metastatic HER2-overexpressing MOC initially underwent surgery for stage IC1 disease followed by surveillance. After recurrence, she underwent optimal cytoreductive surgery and received capecitabine/oxaliplatin. At subsequent recurrence with peritoneal carcinomatosis and inguinal lymphadenopathy, tumor testing demonstrated HER2 overexpression (3+ by IHC).She was treated with single-agent T-DXd and achieved a complete clinical response after six cycles. She completed nine total cycles and remained without evidence of disease for 12 months on a treatment holiday. Upon recurrence, identified by rising CA-125 and CT findings of vaginal cuff nodularity and left-sided lymphadenopathy, T-DXd was restarted. After six additional cycles, CA-125 downtrended and imaging demonstrated decreased disease burden, consistent with a favorable response. Conclusion: This is the first known report of a complete clinical response in HER2-overexpressing MOC treated with T-DXd, including response to rechallenge after recurrence. These findings support further investigation of HER2-directed therapy in this rare and aggressive disease.