Rubinstein MM, Hyman DM, Caird I, et al. - In this single-arm phase 2 study of monotherapy LY3023414, researchers tested the effectiveness and safety of the dual PI3K/mTOR inhibitor, LY3023414, in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway. Qualified individuals had advanced endometrial cancer of any grade, prior management with 1-4 cytotoxic lines, and PI3K pathway activation prospectively defined as a loss-of-function PTEN alteration or activating alteration in PIK3CA, AKT1, PIK3R1, PIK3R2, or MTOR. According to results, 28 individuals have been treated; histologies included endometroid (39%), carcinosarcoma (25%), serous (21%), and mixed (14%). PIK3CA (68%), PTEN (43%), and PIK3R1 (32%) were the most common alterations involved. No association was noted between molecular alterations and response. LY3023414 showed modest single-agent activity and a manageable safety profile in patients with heavily pretreated advanced endometrial cancer prospectively selected for tumors with activating PI3K pathway mutations. Anemia, hyperglycemia, hypoalbuminemia, and hypophosphatemia were the most common all-grade treatment-related adverse events.