Introduction/Background Few data are available of response to chemotherapy in advanced EC (endometrial cancer) patients according to molecular subtypes. Here we present the baseline histo-molecular profile of the platinum-sensitive advanced EC included in the Utola multicenter, randomized phase 2 trial evaluating the efficacy of olaparib as maintenance therapy.

Methodology 147 patients with objective response (OR) or stable disease (SD) after first line platinum chemotherapy were included. IHC (P53 and MMR) and NGS molecular status (including POLE, BRCA1/2 mutations, MSI sensor and genomic instabillity score [G-scar]) were obtained from archived tumor tissue. ESGO molecular subgroups were defined: POLE-mutated, MMR-deficient (MMRd, based on IHC and/or MSI genetic status, without POLE mutation), TP53-mutated based on IHC (without MMRd or POLE mutation) and NSMP (non-specific molecular profile, without MMRd, POLE-mutation nor TP53 mutation).

Results Among 130 evaluable patients, mean age was 69.5 y, 46% were metastatic at the outset, 76% received 6 cycles of platinum chemotherapy. 19% of patients had serous and 75% endometrioid carcinoma (with 32% high grade). 14% were MMRd, 53% TP53-mutated, 33% NSMP and 1 tumor POLE-mutated. NGS for TP53 and MSI status was concordant with IHC in 92% and 99% respectively. Three pathogenic BRCA1/2 mutations were observed in 1 TP53 and 2 MMRd tumors. TP53 tumors had higher GScar mean score (p<0.01). After CT, 68% of the patients had an OR (28% CR), 25% SD and 7% NED. Complete response was different according to molecular subgroups: 75%, 11% and 11% of respectively TP53-mutated, MMRd and NSMP tumors and for the single POLE-mutated tumor.

Conclusion More half of UTOLA tumors are associated with poor prognosis molecular profiles. A high concordance of NGS MSI/P53 and IHC was observed. High platine sensitivity and genomic instability observed in TP53 mutated tumors reinforces the rational to evaluate olaparib in this population.