ESMO E-Learning: Treatment of Advanced or Recurrent Endometrial Cancer

In this E-Learning module the authors elaborate epidemiology and risk factors, genomic characterisation of endometrial cancer, provide standard of care supported by treatment algorithms from the clinical practice guidelines, explore the findings from the clinical trials with endocrine treatment, chemotherapy, immunotherapy, targeted treatments and dig into future perspectives from currently recruiting clinical trials.  

Endometrial cancer is most common gynaecologic cancer in the developed world. Majority (80%) of patients are diagnosed early and 5-year survival rate for early-stage disease is 95%. However, in women with advanced or recurrent endometrial cancer, 5-year survival is 68% in case of regional and 17% in case of distant disease.

The authors start the module by introducing endometrial cancer from the aspect of a global public health burden, as endometrial cancer incidence and mortality have increased annually. The authors underline that global increase in endometrial cancer incidence reflects a change in lifestyle and a higher prevalence of risk factors such as obesity and inactivity levels in younger generations. They explain interaction between obesity and increased endogenous oestrogen production.

In the module the authors present traditional classification of endometrial cancer, as well molecular profiling with potential therapeutic impact.

They further state that in patients with advanced/recurrent endometrial cancer, first-line standard of care treatment includes hormonal therapy or chemotherapy with carboplatin-paclitaxel regimen. There is no standard of care for second-line chemotherapy. Second-line options include pembrolizumab alone or in combination with lenvatinib, and dostarlimab in MMR deficient tumours, and pembrolizumab plus lenvatinib regardless of MMR status. The authors urge that participation in clinical trials should be offered to all patients with relapsed disease.

In phase II setting letrozole/palbociclib showed encouraging results. However, the results with PI3K-mTOR inhibitors are disappointing to date. Dual anti-HER2 treatment demonstrated antitumour activity in heavily pretreated patients. Future research agenda in patients with endometrial cancer includes studies in first-line management of chemotherapy with or without immunotherapy and chemotherapy versus immunotherapy plus anti-VEGF therapy.