A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma

Elizabeth H. Stover, Niya Xiong, Andrea P. Myers, Nabihah Tayob, Victoria Engvold, Madeline Polak, Russell R. Broaddus, Vicky Makker, Ronny Drapkin, Joyce F. Liu, Neil S. Horowitz, Funda Meric-Bernstam, Carol Aghajanian, Robert L. Coleman, Gordon B. Mills, Lewis C. Cantley, Ursula A. Matulonis, Shannon N. Westin, Panagiotis A. Konstantinopoulos

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Uterine serous carcinoma (USC) is an uncommon subtype of endometrial cancer with a poor prognosis. USCs have genomic alterations in the PI3K pathway. A prior phase II study of AKT inhibitor MK-2206 (an allosteric AKT inhibitor, primarily affecting AKT1 and AKT2) in endometrial cancers resulted in progression-free survival (PFS) of ≥6 months in five out of seven patients with USC. To further assess the activity of MK-2206 in USC, we designed a phase II, single-stage assessment of MK-2206 in patients with advanced or recurrent high-grade serous endometrial cancer, who had received up to two lines of prior therapy. MK-2206 (135 mg) was administered orally once per week, in continuous 28-day cycles. Fourteen patients received treatment. The most common treatment-related adverse events were diarrhea (36%), acneiform rash (36%), nausea (29%), fatigue (29%), and hyperglycemia (21%); most events were grade 1–2. One confirmed partial response was observed in a patient who was also alive and progression-free at 6 months. One additional patient was alive and progression-free at 6 months. The clinical benefit rate was 14.3% (95% CI: 1.8 to 42.8). Five patients had stable disease (35.7%) and seven had progressive disease (50%); one was unevaluable. Median PFS was 2 months (95% CI: 1.6 to 4.4) and median overall survival was 6.4 months (95% CI: 5.1 to not reached). In summary, MK-2206 had limited activity in USC, although a few patients achieved sustained progression-free intervals in this study and in the previously reported phase II trial of MK-2206. Further investigations are needed to identify features associated with response.

Original languageEnglish (US)
Article number100974
JournalGynecologic Oncology Reports
Volume40
DOIs
StatePublished - Apr 2022

Keywords

  • AKT inhibitor
  • MK-2206
  • PI3K/AKT pathway
  • Uterine serous carcinoma

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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