Clinicopathologic features and outcomes of patients with microsatellite instability-high endometrial cancer treated with pembrolizumab in Japan: the KCOG-G1902S/1903S study

Objective: To characterize clinicopathologic features of microsatellite instability-high (MSI-high) gynecologic malignancies in Japan and evaluate outcomes of pembrolizumab in MSI-high endometrial cancer, including an exploratory assessment of MLH1 promoter methylation and obesity.Methods: Gynecologic malignancies undergoing routine MSI testing at 11 institutions were registered (KCOG-G1902S).Clinicopathologic data of MSI-high cases were collected from medical records.Patients with MSI-high endometrial cancer treated with pembrolizumab were prospectively followed (KCOG-G1903S).MLH1 promoter methylation was assessed in tumors with MLH1 loss, and exploratory analyses evaluated outcomes according to MLH1 methylation status and body mass index (BMI).Results: Among 529 tumors tested, 56 (10.6%) were MSI-high, most arising in the endometrium (52/251; 20.7%).MSI-high tumors from other organs were predominantly endometrioid.All MSI-high tumors showed mismatch repair protein loss on immunohistochemistry; 41/56 (73.2%) demonstrated PMS2 and/or MLH1 loss.Pembrolizumab was administered to 25 patients with MSI-high endometrial cancer.The objective response rate was 48% (12/25), with median progression-free survival (PFS) of 21.2 months and overall survival