The management of recurrent endometrial tumours includes hormonal therapies for lower-grade and hormone receptor positive tumours, while platinum-based chemotherapy regimens are given as the first-line treatment for recurrent higher-grade subtypes. Second and subsequent line treatments include chemotherapeutic and other hormonal agents, all with limited response rates of approximately 15% or less.

There is a clear need to explore novel therapeutic options in this tumour type. Our recognition of the interplay between tumour cells and the immune system has evolved, and we now know that the evasion of normal immunological recognition and control is central in tumorigenesis and metastasis. PD-L1 is part of the B7/CD28 family and is a ligand for the death receptor programmed death receptor 1 (PD-1). The interaction between PD-1 and PD-L1 inhibits memory T cells in the periphery, protecting them from immune regulatory controls and destruction.

In endometrial cancers, cytoplasmic PD-L1 expression has been reported in up to 92% of tumours, particularly MMR (mismatch repair) deficient and Type II subsets, where the tumour mutation load is expected to be higher. Thus, there is a strong rationale for the exploratory use of immune checkpoint inhibitors for these tumour types, particularly when current therapeutic options remain dismal. PHAEDRA is utilising durvalumab (MEDI 4736) to assess its effect on women with advanced endometrial cancer (both MMR-proficient and deficient) and the subsequent tumour response to immune checkpoint inhibition.

See ANZCTR for full trial details >