当前位置： SCI文献检索 > GYNECOLOGIC ONCOLOGY期刊下所有文献 > Results from a single arm, single stage phase II trial of trametinib and GSK2141795 in persistent or recurrent cervical cancer.

Results from a single arm, single stage phase II trial of trametinib and GSK2141795 in persistent or recurrent cervical cancer.

Abstract：

BACKGROUND:Improved treatment for advanced cervical cancer is needed; currently, treatment options include combined chemotherapy and bevacizumab or pembrolizumab monotherapy for PD-L1 positive disease. PIK3CA and KRAS mutations have been reported in cervical cancers; this study therefore tested dual inhibition of PI3K and RAS signaling by combining the MEK inhibitor trametinib and the AKT inhibitor GSK2141795 in recurrent cervical cancer. METHODS:This was an investigator-initiated phase II study combining trametinib and GSK2141795 in patients with recurrent cervical cancer. Primary endpoint was best tumor response; secondary endpoints included progression free survival, overall survival, and safety assessment. Translational objectives included characterization of molecular alterations in PI3K and RAS signaling pathway genes. RESULTS:Planned accrual was 35 patients; 14 patients were enrolled and received at least one dose of study drug before the study was terminated due to discontinuation of GSK2141795 development. There were no confirmed responses; 1 patient had an unconfirmed PR, 8 had stable disease, 3 had progression as best response, and 2 were unevaluable. Toxicities were mostly grade 1 and 2, although 57% of patients experienced grade 3/4 adverse events and 50% patients required a dose reduction. CONCLUSIONS:The combination of trametinib and GSK2141795 was feasible but required dose holds and modifications for adverse events; however, anti-cancer activity was minimal, even in patients with PI3K or RAS pathway alterations. Although the study was terminated early after GSK2141795 development was halted, the findings in these 14 patients do not support further development of this combination in cervical cancer.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Liu JF,Gray KP,Wright AA,Campos S,Konstantinopoulos PA,Peralta A,MacNeill K,Morrissey S,Whalen C,Dillon D,Matulonis UA

doi

10.1016/j.ygyno.2019.05.003

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

95-101

issue

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(19)31228-4

journal_volume

154

pub_type

杂志文章,多中心研究

在线工具

Results from a single arm, single stage phase II trial of trametinib and GSK2141795 in persistent or recurrent cervical cancer.