LOCALLY ADVANCED OR METASTATIC ENDOMETRIAL CANCER IN 2025: WHAT SYSTEMIC MANAGEMENT STRATEGIES BEYOND FIRST-LINE?

Abstract

Endometrial cancer is one of the most common gynecologic malignancies, primarily affecting post menopausal women. While most cases are diagnosed at an early stage, approximately 10- 15% progress to metastatic or recurrent disease, associated with a poor prognosis. Since 2023, chemoimmunotherapy has become the standard first-line treatment, particularly with the addition of PD-1/PD-Ll inhibitors to carboplatin-paclitaxel chemotherapy. However, second line and beyond therapeutic strategies remain crucial for improving patient survival.

In the second-line setting, the lenvatinib-pembrolizu mab combination has demonstrated significant benefits in progression-free and overall survival compared to standard chemotherapy, although its efficacy after first-line immunotherapy remains to be determined. Doxorubicin and hormone therapy remain options, though with limited efficacy. Emerging therapeutic approaches include antibody-drug conjugates (ADCs) targeting HER2, Trop2, and FRα, which have shown promising objective response and disease control rates. Additionally, novel immune checkpoint inhibitors targeting LAG-3, TIGIT, and TIM-3, as well as innovative combinations involving cellular therapy and therapeutic vaccines, are currently under clinical investigation.
The future of advanced endometrial cancer treatment relies on optimizing therapeutic sequencing and identifying predictive biomarkers to personalize systemic management strategies.