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

Daniel Ahn, Junan Li, Lai Wei, Austin Doyle, John L. Marshall, Larry J. Schaaf, Mitch A. Phelps, Miguel A. Villalona-Calero, Tanios Bekaii-Saab

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Abstract

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.

Original languageEnglish (US)
Article number12122
JournalScientific Reports
Volume5
DOIs
StatePublished - Jul 10 2015
Externally publishedYes

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Biliary Tract Neoplasms
Pharmacokinetics
Cytotoxins
MK 2206
Patient Selection
Drug Therapy

ASJC Scopus subject areas

  • General

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Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer. / Ahn, Daniel; Li, Junan; Wei, Lai; Doyle, Austin; Marshall, John L.; Schaaf, Larry J.; Phelps, Mitch A.; Villalona-Calero, Miguel A.; Bekaii-Saab, Tanios.

In: Scientific Reports, Vol. 5, 12122, 10.07.2015.

Research output: Contribution to journalArticle

Ahn, Daniel ; Li, Junan ; Wei, Lai ; Doyle, Austin ; Marshall, John L. ; Schaaf, Larry J. ; Phelps, Mitch A. ; Villalona-Calero, Miguel A. ; Bekaii-Saab, Tanios. / Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer. In: Scientific Reports. 2015 ; Vol. 5.
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