Real-world evidence of Trastuzumab Deruxtecan (T-DXd) Efficacy in HER2-expressing gynecological malignancies

Abstract

Human epidermal growth factor receptor 2 (HER2) overexpression emerges as an attractive therapeutic target in gynecological malignancies. Recently, Trastuzumab-Deruxtecan (T-DXd) has shown substantial efficacy in HER2 overexpressing carcinomas, most prominently in ovarian, endometrial and cervical patients. We have examined the efficacy of T-DXd in patients with metastatic endometrial, ovarian and cervical malignancies that were treated in the Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens.MethodsPatients with gynecological malignancies with HER2 expression 2 + /3 + as assessed by immunohistochemistry (IHC) that were treated with T-DXd were retrospectively identified. Patients received T-DXd intravenously at a dose of 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity.ResultsIn total, 10 patients treated with T-DXd for recurrent/metastatic disease were identified. Regarding histology, there were 5 patients with uterine neoplasms (serous carcinoma (n = 3), uterine carcinosarcoma (n = 1), uterine leiomyosarcoma (n = 1)), 1 patient with squamous cervical carcinoma and 4 patients with ovarian cancer (ovarian carcinosarcoma (n = 2), high-grade serous carcinoma (n = 1) and mucinous ovarian carcinoma (n = 1)). Median age was 65.4 years (25th-75th percentile, 58.1-75.2 years). 5 patients had HER2 expression 3 + by IHC and 5 patients had HER2 expression 2 + . Median number of previous lines of therapy was 4 (range 2-6), 2 patients with uterine serous carcinoma were pretreated with trastuzumab and 4 patients had already received immunotherapy. In the entire cohort median progression-free survival (PFS) was 5.4 months (95%CI 0.8-9.8 months). Regarding responses, 5 patients had partial response (including 2 patients that were pretreated with trastuzumab), 1 patient had stable disease at 12 weeks and 4 patients had disease progression at initial assessment. All patients but one that derived clinical benefit had HER2 3 + expression.DiscussionIn the real-world setting, T-DXd showed activity in a cohort of heavily pre-treated patients with HER2-expressing gynecological malignancies.

Keywords: DS-8201; Endometrial cancer; Gynecologic cancer; HER2; Ovarian cancer; T-DXd; Trastuzumab deruxtecan.