TY - JOUR
T1 - A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma
AU - Stover, Elizabeth H.
AU - Xiong, Niya
AU - Myers, Andrea P.
AU - Tayob, Nabihah
AU - Engvold, Victoria
AU - Polak, Madeline
AU - Broaddus, Russell R.
AU - Makker, Vicky
AU - Drapkin, Ronny
AU - Liu, Joyce F.
AU - Horowitz, Neil S.
AU - Meric-Bernstam, Funda
AU - Aghajanian, Carol
AU - Coleman, Robert L.
AU - Mills, Gordon B.
AU - Cantley, Lewis C.
AU - Matulonis, Ursula A.
AU - Westin, Shannon N.
AU - Konstantinopoulos, Panagiotis A.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - AKT inhibitor
KW - MK-2206
KW - PI3K/AKT pathway
KW - Uterine serous carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85127505695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127505695&partnerID=8YFLogxK
U2 - 10.1016/j.gore.2022.100974
DO - 10.1016/j.gore.2022.100974
M3 - Article
AN - SCOPUS:85127505695
SN - 2211-338X
VL - 40
JO - Gynecologic Oncology Reports
JF - Gynecologic Oncology Reports
M1 - 100974
ER -