A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor Positive Metastatic Breast Cancer

摘要

PurposePhosphatidylinositol-3-kinase (PI3K)/AKT pathway activation is an important endocrine resistance mechanism in estrogen receptor positive (ER+) breast cancer. After promising preclinical modeling of MK-2206, an allosteric pan-AKT inhibitor, with either estrogen-deprivation or fulvestrant, we conducted a Phase 1 trial in patients with metastatic ER+HER2− breast cancer to determine the recommended phase II treatment dose (RPTD) of MK-2206 when combined with either anastrozole, fulvestrant, or anastrozole/fulvestrant.