Introduction
cancer, tumour, gynaecologic malignancy
ENDOMETRIAL CARCINOMA, CANCER, TUMOUR, BLOOD
Endometrial carcinoma (EC) is the gynaecologic malignancy with highest incidence and remains the fourth most common cancer diagnosis in North American womenA single-arm phase I trial assessing treatment with the PD-1 inhibitor dostarlimab (NCT02715284) demonstrated an objective response rate (ORR) of 42.3% (95% confidence interval [CI] 31–55%) in 104 women with MMRd recurrent or advanced EC previously treated with platinumA randomized phase III trial (NCT03517449) compared pembrolizumab and lenvatinib to single agent chemotherapy in patients with EC previously treated with platinumOther potential combination therapies with ICI in EC include DNA damaging agents. Preclinical studies have shown synergy between combining a PARP inhibitor and ICIDefining the molecular vulnerabilities of recurrent EC may guide treatment strategy. Blood based biomarkers have shown the potential of capturing multiclonal heterogeneity over time in certain tumour sites. To our knowledge, the potential of ctDNA to monitor the tumour evolution and as a biomarker for treatment selection has not yet been described in EC.In this work we assess whether the PARP inhibition approach with niraparib, or the combination of niraparib and dostarlimab, provides clinical benefit in patients with recurrent EC. Exploratory analyses include immunohistochemistry (IHC), genomic and ctDNA-based biomarker analysis, and association between a ctDNA-based genomic panel with tissue profiling