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Sci Rep. 2015 Jul 10;5:12122. doi: 10.1038/srep12122.

Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer.

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Divison of Medical Oncology, Ohio State University Comprehensive Cancer Center, 300 W 10th Ave, Columbus, OH 43210.
College of Pharmacy, Ohio State University, 500 W 12th Ave, Columbus, OH 43210.
Center of Biostatistics, Ohio State University, 300 W 10th Ave, Columbus, OH 43210.
Cancer Therapy Evaluation Program, National Cancer Institute, 9609 Medical Center Dr, Bethesda, MD 20892.
Division of Hematology/Oncology, Lombardi Comprehensive Cancer Center, 3800 Reservoir Rd, Washington, DC 20057.


Biliary cancers (BC) are rare, chemoresistant and are associated with a poor prognosis. Targeting the Akt pathway is of significance in BC. We hypothesized that the allosteric inhibitor MK-2206 will be active in BC. This was a multi-institutional phase II study of MK-2206 given to patients with advanced, refractory BC. The primary end point was overall response rate. We also characterized pharmacokinetic profiles of MK-2206 in these patients and explored its potential correlation with clinical outcomes. Eight patients were enrolled prior to early termination of the trial. All patients had received prior systemic therapy. The best response observed was stable disease, exceeding 12 weeks in two patients. Toxicities were mild and tolerable. MK-2206 exhibited a pharmacokinetic profile with an apparent slow absorption followed by biphasic elimination in these patients with BC. No significant association was observed between the pharmacokinetic properties of MK-2206 and clinical outcomes. MK-2206 as a single-agent in BC is tolerable with pharmacokinetic properties similar to patients with other solid tumors. No clinical activity was observed in this limited population. Further development of Akt inhibitors may need to focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy and prospective patient selection.

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