Current approaches to first-line therapy for endometrial cancer: the role of lenvatinib and pembrolizumab combination therapy

Endometrial cancer (EC) remains the most common gynecologic oncology disease in Russia, with a tendency toward increasing incidence and associated mortality. In recent years, significant progress has been made in understanding the molecular mechanisms underlying the disease, leading to the development of a molecular classification of EC, which has enabled the implementation of personalized treatment approaches. Determining the status of microsatellite instability (MSI) and deficiency in the mismatch repair system (dMMR), as well as identifying mutations in the POLE and TP53 genes, has become a key component in diagnosis and decision-making regarding therapy.The combination of lenvatinib and pembrolizumab has demonstrated clinical efficacy in pMMR / MSS EC in the second-line setting. The Study 309 and LEAP-001 trials confirm the clinical benefit of lenvatinib and pembrolizumab in patients with pMMR / MSS tumor phenotypes following prior systemic therapy. Expert consensus highlights the necessity of testing all patients for dMMR / MSI at initial EC diagnostics and supports the early use of immunotargeted therapy with lenvatinib and pembrolizumab already in the setting for patients with pMMR / MSS phenotype and prior adjuvant systemic therapy. The aim of this review is to analyze current approaches to systemic therapy for EC, assess the clinical significance of lenvatinib and pembrolizumab therapy, and examine the role of molecular diagnostics in guiding treatment decisions.