Evolution of systemic therapy for disseminated endometrial cancer: literature review

The TC combination regimen (paclitaxel + carboplatin) is the “gold standard” first-line therapy for disseminated endometrial cancer (EC). The use of hormone therapy (HT) in the first-line setting is limited. Until recently, patients with disseminated EC had unfavorable outcomes despite the standard-of-care treatment (chemotherapy (CHT) and HT). None of the available cytostatics could improve disease control and survival in patients who have received standard platinum-based therapy. Evidently, the poor treatment outcomes of disseminated EC suggested that therapeutic approaches should be changed, and more effective treatment regimens should be developed. The treatment of disseminated EC has been revolutionized with deeper understanding of carcinogenesis, a new molecular classification of EC, and stratification of treatment approaches according to the biological potential of the tumor. The most significant advances included understanding the role of microsatellite instability (MSI) and DNA mismatch repair (MMR) deficiencies as a predictor of high efficacy of immunotherapy, a novel class of systemic therapies for disseminated EC. This review article focuses on the evolution of systemic therapy for disseminated EC. Here we discuss in detail the results of key international trials of HT, first and second lines of chemotherapy, targeted therapy, immunotherapy, and immunotherapeutic/ targeted agents for disseminated EC. Biological markers, such as MSI and PD-L1, their correlation with the response rate, and the mechanism of synergy between pembrolizumab and lenvatinib are discussed in detail.