Complete response to trastuzumab-deruxtecan (Enhertu, T-DXd) in HER2-positive stage IVB uterine carcinosarcoma.

Objectives: To report a case of complete response to trastuzumab-deruxtecan (T-DXd) in a patient with HER2-positive stage IVB uterine carcinosarcoma, and to contextualize this within evolving therapy for HER2-positive gynecologic malignancies. Methods: We present the clinical course of a 62-year-old woman with a history of multiple prior malignancies, diagnosed with stage IVB uterine carcinosarcoma exhibiting HER2 overexpression. Following optimal cytoreductive surgery and first-line carboplatin, paclitaxel, and trastuzumab, the patient developed platinum-resistant recurrence. She was subsequently treated with T-DXd, and received serial imaging and clinical monitoring. Results: The patient achieved a partial response by cycle 4 of T-DXd, with subsequent scans demonstrating a complete response with no evidence of disease. She has successfully completed 21 cycles of T-DXd with minimal toxicity, aside from a reversible acute kidney injury and a small pleural effusion, both resolving without sequelae. The patient remains asymptomatic and continues therapy without any cardiopulmonary complications. Conclusions: This case highlights the efficacy of T-DXd for HER2-positive, platinum-resistant uterine carcinosarcoma, even when previously treated with Trastuzumab. Highly durable, complete response with manageable toxicity was achieved, underscoring the promise of T-DXd.