Adding trastuzumab to carboplatin and paclitaxel improves overall survival in patients with advanced-stage HER2/neu-overexpressing uterine serous carcinoma or carcinosarcoma

Abstract Background Uterine serous carcinomas and carcinosarcomas are aggressive forms of endometrial cancer with poor survival outcomes. Trastuzumab, a human epidermal growth factor receptor-2 (HER2)-directed monoclonal antibody, has demonstrated tumoricidal efficacy. However, clinical data regarding its efficacy in uterine serous carcinoma are limited, and there are no clinical data available for uterine carcinosarcoma. Therefore, this study aimed to ascertain the efficacy and safety of adding trastuzumab to carboplatin and paclitaxel as a frontline treatment for advanced-stage HER2-overexpressing uterine serous carcinoma and carcinosarcoma. Methods This retrospective study used deidentified data from electronic health records sourced from the TriNetX Research Network. Participants were identified using ICD codes, and HER2 positivity was confirmed by immunohistochemistry or fluorescence in situ hybridisation (FISH). Propensity score matching (PSM) was employed to reduce confounders, and survival outcomes and adverse events were assessed. Results Following PSM, 280 patients with advanced HER2-positive uterine serous carcinoma or carcinosarcoma were analysed. The group of patients treated with carboplatin/paclitaxel + trastuzumab (CP + T) showed a significantly extended median overall survival compared to those treated solely with CP (41 months versus 25.2 months, hazard ratio [HR] = 0.51, p = 0.002) in both advanced-stage uterine carcinosarcoma and serous carcinoma. Specifically, patients with uterine carcinosarcoma experienced an even longer survival benefit (HR = 0.39, p < 0.0001) when trastuzumab was added to their chemotherapy regimen, surpassing the survival benefit seen in patients with uterine serous carcinoma (HR = 0.56, p = 0.04). However, patients who received trastuzumab experienced higher rates of hypertension, diarrhoea, and left ventricular systolic dysfunction. Conclusions The addition of trastuzumab to frontline chemotherapy is effective for the treatment of HER2-overexpressing uterine serous carcinoma and carcinosarcoma, particularly uterine carcinosarcoma. However, careful monitoring of adverse cardiac events is needed.