Schmid P, Zaiss M, Harper-Wynne C, et al. - In postmenopausal women with estrogen receptor–positive advanced or metastatic breast cancer, researchers tested the effectiveness and safety of vistusertib in combination with fulvestrant vs fulvestrant alone or fulvestrant plus everolimus. In the MANTA trial, an open-label, phase 2 randomized clinical trial, randomization of 333 patients with estrogen receptor–positive breast cancer progressing after prior aromatase inhibitor treatment (2:3:3:2) was done at 88 sites in 9 countries: 67 patients were assigned to receive fulvestrant, 103 fulvestrant plus vistusertib daily, 98 fulvestrant plus vistusertib intermittently, and 65 fulvestrant plus everolimus. This trial failed to show a benefit of vistusertib plus fulvestrant vs fulvestrant alone. Furthermore, both vistusertib groups vs the group treated with fulvestrant plus everolimus had inferior outcomes.