Adaptively Randomized Trial Of Neoadjuvant Chemotherapy With Or Without The Akt Inhibitor Mk-2206: Graduation Results From The I-Spy 2 Trial.

524 Background: A key node of growth and survival signaling pathways is the Akt serine/threonine kinase that activates mTOR and downstream effectors. I-SPY 2 is a randomized neoadjuvant trial to test agents and combinations added to standard chemotherapy. Pathological complete response (pCR) defined as absence of invasive cancer in breast and nodes is the primary endpoint. We report efficacy results for allosteric Akt inhibitor MK-2206. Methods: Women with invasive breast cancer ≥2.5 cm on exam or ≥2 cm on imaging were adaptively randomized to 12 weekly paclitaxel (and trastuzumab if HER2+) cycles (control) or in combination with one of several experimental agents followed by doxorubicin/cyclophosphamide x 4. Patients (pts) are stratified to 8 subsets based on hormone-receptor (HR), HER2, and MammaPrint statuses, with combinations of subsets defining agent signatures. MK-2206 135 mg daily by mouth was evaluated in all 8 subsets. Adaptive assignment to the experimental arms was based on current Bayesian pr...