Emerging therapies in gynaecological cancers (part 2): Endometrial cancer - Adjuvant and metastatic settings

Historically, the treatment of patients with advanced and metastatic endometrial cancers (ECs) included a limited number of systemic therapeutic options. The identification of four distinct molecular subgroups through the TCGA classification has significantly improved the understanding of this disease and enabled the development of new treatments. Around 25-30% of ECs are known to have a MSI-H/MMRd status and are characterised by high PD-L1 expression and strong CD8+ T cell infiltration, explaining their remarkable
sensitivity to immune checkpoint inhibitors (ICIs). Indeed, these therapies have demonstrated high response rates and significant survival benefits, redefining the standard of care in both first-line and recurrent settings.
In contrast, 70-75% of ECs have a MSS/MMRp status, including a heterogeneous population and thus exhibiting more variable responses to ICIs. Furthermore, emerging approaches include the use of antibody-drug conjugates targeting proteins that are overexpressed in tumour cells and often linked to poor prognosis, such as Trop-2 and HER2. Selinexor, an exportin 1 (XPO1) inhibitor inducing nuclear accumulation of key
proteins and leading to tumour cell death, is another innovative strategy.