Evolution of Systemic Therapies in Endometrial Cancer: From Cytotoxic Chemotherapy to Immunotherapy, Targeted Therapies, and Antibody–Drug Conjugates
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Abstract
Molecular classification in endometrial cancer (EMC) has become central to treatment decision-making. An advance in molecular classification has transformed the therapeutic landscape of EMC, particularly in patients with high-risk, advanced, or metastatic disease. This coincided with a new era of personalized treatment with targeted therapies, immunotherapy in particular, immune checkpoint inhibitors (ICIs). Several studies have demonstrated the benefits of combination strategies incorporating chemotherapy, targeted therapies, and ICIs with or without tyrosine kinase inhibitor, followed by maintenance therapy. This approach has resulted in clinically meaningful improvements in progression free survival and, in selected populations, overall survival, with the most pronounced benefit observed in mismatch repair (MMR)–deficient tumors. This review summarizes current evidence from pivotal phase II-III trials evaluating ICIs combined with chemotherapy, ICIs with poly adenosine diphosphate ribose polymerase inhibitors, and targeted agents including trastuzumab, bevacizumab, and selinexor as first- and second-line treatment for EMC. Studies of antibody-drug conjugates, novel therapeutic agents designed to selectively deliver cytotoxic drugs and thereby reduce the systemic toxicity associated with chemotherapy, were also included. Treatment recommendations are summarized within the context of MMR status, p53 abnormalities, human epidermal growth factor receptor 2/neu expression, and other emerging molecular biomarkers.
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