A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma Journal Article
| Authors: | Stover, E. H.; Xiong, N.; Myers, A. P.; Tayob, N.; Engvold, V.; Polak, M.; Broaddus, R. R.; Makker, V.; Drapkin, R.; Liu, J. F.; Horowitz, N. S.; Meric-Bernstam, F.; Aghajanian, C.; Coleman, R. L.; Mills, G. B.; Cantley, L. C.; Matulonis, U. A.; Westin, S. N.; Konstantinopoulos, P. A. |
| Article Title: | A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma |
| 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. © 2022 The Authors |
| Keywords: | pi3k/akt pathway; uterine serous carcinoma; mk-2206; akt inhibitor |
| Journal Title: | Gynecologic Oncology Reports |
| Volume: | 40 |
| ISSN: | 2352-5789 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2022-04-01 |
| Start Page: | 100974 |
| Language: | English |
| DOI: | 10.1016/j.gore.2022.100974 |
| PROVIDER: | scopus |
| PMCID: | PMC9011027 |
| PUBMED: | 35434236 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
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