Journal article
A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study
Gynecologic Oncology, Vol.138(1), pp.30-35
07/2015
DOI: 10.1016/j.ygyno.2015.04.005
PMCID: PMC4469526
PMID: 25887099
Abstract
Activation of the mitogen activated protein kinase pathway plays a pivotal role in cell proliferation and is frequently activated in endometrial cancer. We sought to evaluate the efficacy/safety of selumetinib, a selective MEK-1/2 inhibitor in women with recurrent endometrial cancer. This was a phase II, single-arm, open-label study evaluating response and 6-month event-free survival (EFS) as primary endpoints. Eligible patients had measurable disease, 1-2 prior cytotoxic regimens, and performance status 0-2. Selumetinib 75mg PO BID was administered daily until progression or intolerance. One cycle was 28days. Fifty-four patients were enrolled; 2 were excluded due to improper pre-study treatment (1) and never treated (1), leaving 52 evaluable for efficacy/safety. Median age was 62; histology included endometrioid (58%), serous (17%) and mixed (23%). Seventeen patients (33%) had 2 prior cytotoxic regimens. The median number of cycles administered was 2 (1-34). Three (6%) patients had objective response (1 CR, 2 PR); 13 had SD as best response. The proportion of patients with 6-month EFS was 12%. Median EFS, progression-free and overall survival was 2.1, 2.3, and 8.5months, respectively. Drug-attributed grade 3/4 adverse events were observed (≥5%) were fatigue (15%), anemia (10%), pain (10%), extremity edema (8%), and dyspnea (6%). There was 1 grade 4 infection (renal), 1 grade 4 anemia, and 1 death due to hemorrhage (rectum). Selumetinib was tolerable in this population but did not meet pre-trial specifications for clinical efficacy. •Selumetinib, a MEK inhibitor was tolerable in recurrent endometrial cancer patients•Objective responses were observed in 6% of patients•The most significant drug-related severe adverse events were fatigue, anemia and pain.
Details
- Title: Subtitle
- A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study
- Creators
- Robert L Coleman - Dept. of Gynecologic Oncology & Reproductive Medicine, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030Michael W Sill - NRG Oncology Statistics & Data Management Center; Roswell Park Cancer Institute, Buffalo, NY 14263Premal H Thaker - Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, MO 63110David P Bender - University of Iowa; Gyn/Onc Division; Iowa City, IA 52242Daron Street - Cancer Care Associates; Tulsa, OK 74136William P McGuire - Franklin Square Hospital; Medical Oncology; Baltimore, MD 21237Carolyn M Johnston - Division. of Gynecologic Oncology; University of Michigan; Ann Arbor, MI 48109Jacob Rotmensch - Rush-Presbyterian St. Lukes Med. Center; Chicago, IL 60612
- Resource Type
- Journal article
- Publication Details
- Gynecologic Oncology, Vol.138(1), pp.30-35
- DOI
- 10.1016/j.ygyno.2015.04.005
- PMID
- 25887099
- PMCID
- PMC4469526
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Grant note
- 1 U10 CA180822 / NRG Oncology CA 27469 / Gynecologic Oncology Group Administrative Office CA 37517 / Gynecologic Oncology Group Statistical and Data Center National Cancer Institute (http://dx.doi.org/10.13039/501100002387)
- Language
- English
- Date published
- 07/2015
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983930273502771
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