| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Gynecologic Oncology Reports, Vol 40, Iss , Pp 100974- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2352-5789 |
| DOI: |
10.1016/j.gore.2022.100974 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
