Introduction/Background Molecular genetic subtyping of uterine cancer has attracted attention for treatment selection. This study aims to clarify the clinical characteristics of molecular genetic subtyping in endometrial cancer and the relationship to the efficacy of immune checkpoint inhibitor (pembrolizumab) mono or in combination with lenvatinib (LP) for recurrent uterine cancer.

Methodology In two cohorts of the patients who underwent surgery for uterine cancer in our department between 2006 and 2011, and the patients who were treated with pembrolizumab for recurrent uterine cancer in 2019 or later, gene targeted sequencing and mismatch repair (MMR)-related immunostaining, were performed to identify POLE-mutated (POLE), microsatellite instability high (MSI), copy number high (CNH), and nonspecific molecular profile (NSMP) subtypes.

Results First, 104 patients (pts) who underwent surgery at our department were classified into 24pts with POLE, 20 pts with MSI, 22pts CNH and 30pts with NSMP. POLE had much favorable prognosis with a 0% recurrence rate, while CNH had the poorest prognosis, as previously reported. Next, in the 14 pts with recurrent endometrial cancer, including 8 patients received PEM alone (all for MSI/MMRd) and 6 patients received LP therapy. And in second cohort, overall response rate by molecular genetic subtype were as follows; 50% (4/8 pts) in MSI, 75% (3/4) in CNH, 1% (1/1) in NSMP, and 0 patient in POLE . One case could not be classified.

Conclusion Selecting PEM mono/combination therapies according to molecular genetic subtype classification are useful for the pts with recurrent endometrial cancer.

Disclosures JH has COI about Lecture Fee from MSD, resaerch grant from Chugai, Sumitomopharma, Ono.