Endometrial cancer — cancer of the uterine lining — is the most common gynecologic cancer in developed countries and is rising in incidence, partly linked to increasing obesity rates. Most cases are caught early when surgery is curative, but advanced or recurrent disease has historically had limited options.
What's actually going on in research
Checkpoint immunotherapy has become a cornerstone for mismatch repair-deficient (MSI-H/dMMR) endometrial cancers, and pembrolizumab-based combinations have improved outcomes broadly across molecular subtypes. Antibody-drug conjugates targeting HER2 and other surface proteins are showing strong activity in specific subtypes. Molecular classification — into POLE-mutated, dMMR, copy-number-low, and copy-number-high groups — now guides treatment decisions and is a major focus of ongoing trials.
Checkpoint immunotherapy
PD-1 inhibitors are now combined with chemotherapy as standard therapy for advanced endometrial cancer, with particularly strong responses in dMMR tumors. Trials are testing them in earlier-stage disease.
Antibody-drug conjugates
Drugs targeting HER2, folate receptor alpha, and other proteins overexpressed in endometrial cancer are in active trials, offering options for platinum-resistant and recurrent disease.
Molecular subtype treatment
Trials are prospectively testing whether POLE-mutated and other specific subtype patients can safely de-escalate treatment, and whether FGFR3-targeted drugs benefit the copy-number-high group.
What to know before you search
Eligibility depends on stage, molecular subtype (POLE, dMMR, FGFR3), HER2 status, and prior platinum-based chemotherapy.
What types of trials are currently open
- Treatment trials — Testing new drug combinations or immunotherapy for advanced, recurrent, or metastatic endometrial cancer.
- Adjuvant trials — Testing post-surgery chemotherapy, radiation, or immunotherapy for high-risk early-stage disease.
- Molecular subtype trials — Testing de-escalation or targeted therapy based on molecular classification.
- Surgical trials — Comparing minimally invasive surgical approaches and sentinel lymph node biopsy techniques.
- Supportive care trials — Managing sexual function, lymphedema, and other treatment effects.
Recently added Endometrial Cancer trials
The Surveillance, Epidemiology, and End Results Database Program on Endometrial Cancer in the Italian Population
The aim of this study is to lay the bases for an ambitious project that reports and records all the epidemiological-clinical information of the cases of endometrial carcinoma diagnosed and treated in the reference oncology centers involved on the national territory, to create a process of analysis of the data
REal Word aPpLicAtion of Molecular Based Endometrial Cancer Classification
Despite the high incidence, endometrial cancer represents a low mortality neoplasma due to the high prevalence of early-stage diagnosis (90%). Concerning the uterine-confined disease (FIGO 2009 and 2023 stage I-II), molecular-based classification has showed an unprecedent impact on the treatment algorithm leading to a full integration into the latest staging classification. The first evidence of the prognostic value of molecular subgroups came from the TCGA data in which patients were subdivided into: patients with POLE gene alterations, MMR deficient (MMRd), patients with TP53 gene mutations, absence of one of these alterations (NSMP). The use of molecular classification reveals distinct prognostic groups ranging from an excellent prognosis (POLE mutated) to those with a worst prognosis (p53 mutated). Therefore, according to the ESGO guidelines, in patients with stage I-II POLE mutated endometrial cancer, the recurrence rate is so low as to justify omitting adjuvant treatment in favor of observation alone. Several groups have applied a diagnostic algorithm using five immunohistochemical markers (p53, MLH1, MSH2, MSH6 and PMS2) and a molecular test (analysis of mutations in the exonuclease domain of POLE) to identify prognostic groups similar to the molecular classification of TCGA. The feasibility of this approach has been confirmed by many publications that have all consistently reported prognostic relevance especially in high-grade and high-risk tumours in several independent cohorts and prospective clinical trials. In conclusion, despite the validation of immunohistochemical evaluation in place of molecular evaluation, the need to perform a more complex evaluation to define POLE status makes its implementation not yet ubiquitous. The integration of molecular analysis of the POLE mutations remains challenging across the centers involved in the management of endometrial cancer. REPLACE is a national, cross-sectional survey that will census all Italian gynaecology centres (≈ 264) involved in the endometrial cancer treatment into: (i) quantify POLE testing adoption, (ii) describe diagnostic methodologies, (iii) map treatment de-escalation strategies triggered by POLE status, and (iv) explore management pathways where POLE is unavailable. Findings will highlight implementation gaps and inform future network initiatives.
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