Optimising treatment selection in advanced endometrial cancer

The management of advanced and recurrent endometrial cancer has evolved with the recognition of its molecular heterogeneity. Data from The Cancer Genome Atlas (TCGA) have established distinct molecular subtypes with different prognostic and therapeutic implications, now fully integrated into ESGO guidelines and clinical practice. 

In this video, Prof. Domenica Lorusso provides a concise, guideline-based overview of how molecular classification and clinical trial data inform treatment selection in advanced endometrial cancer. 

The programme explores: 

• The clinical relevance of molecular subtypes and their role in risk stratification and treatment planning 
• ESGO-recommended treatment algorithms for advanced or recurrent disease, including distinctions between dMMR and non-dMMR tumours 
• The positioning of pembrolizumab plus lenvatinib as a chemotherapy-free option in selected patients 
• Established systemic treatment strategies, including chemotherapy–immunotherapy combinations and chemotherapy–immunotherapy–PARPi approaches across molecular subgroups 

Explore the video and slides to deepen your understanding of current treatment guidelines and how they translate into everyday clinical decision-making for advanced endometrial cancer. 

Clinical takeaways

• For advanced/recurrent non-dMMR (pMMR) endometrial cancer, ESGO guidelines recommend ICI + chemotherapy followed by maintenance ICI ± PARPi. When chemotherapy is contraindicated, LEN/PEMBRO is recommended, provided the patient has received prior [neo]adjuvant chemotherapy 
• Chemotherapy contraindications may arise from clinical factors (e.g. severe comorbidities, hematologic dysfunction, ECOG PS >2), prior chemotherapy exposure, or patient-centred reasons (e.g. efficacy–safety considerations, informed refusal). However, as guidelines offer no clear definition, decisions remain at the clinician’s discretion
• During LEN/PEMBRO, close monitoring and grade-based management of key toxicities (thyroid dysfunction, hypertension, diarrhoea, proteinuria and immune-related AEs) support ongoing treatment in most patients. Use supportive care and dose modification for mild–moderate events, corticosteroids for immune-mediated AEs, and permanent discontinuation for severe or persistent toxicity