Presentation Abstract

Abstract Number: CT-05
Presentation Title: A phase II trial of selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum
Presentation Time: Monday, Apr 02, 2012, 3:05 PM - 3:25 PM
Location: McCormick Place West (Level 1), Room W183 B/C
Author Block: John H. Farley1, William E. Brady2, Michael J. Birrer3, Heather Lankes2, Robert Coleman4, Mark Morgan5, Robert Mannel6, Diane Yamada7, David Mutch8, William H. Rodgers9, David M. Gershenson4. 1St. Joseph's Hospital and Medical Center, a member of Catholic Healthcare West, Phoenix, AZ; 2Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY; 3Massachusetts General Hospital, Boston, MA; 4Dept. of Gynecologic Oncology; University of Texas; MD Anderson Cancer Center, Houston, TX; 5Fox Chase Cancer Center, Philadelphia, PA; 6University of Oklahoma Health Sciences Center, Oklahoma City, OK; 7University of Chicago Section of Gynecologic Oncology, Chicago, IL; 8Washington University School of Medicine Department of OB/GYN, St Louis, MO; 9Lenox Hill Hospital Department of Pathology, New York, NY
Abstract Body: Background: This study evaluated selumetinib (AZD6244, ARRY-142866) , an inhibitor of MEK-1/2, and explored associations between RAS/RAF mutations with clinical outcome.
Methods: Women with recurrent low-grade serous ovarian or peritoneal carcinoma were eligible and received selumetinib at 100 mg orally BID until progression or toxicity. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST v 1.0. BRAF, KRAS, and NRAS mutational analysis was performed.
Results: Between December 2007 and November 2009, 52 patients were enrolled. Fifty-eight percent of patients had received at least 3 prior chemotherapy regimens. Eight patients (15.4%) had complete (1) or partial (7) responses, and 34 (65%) had stable disease. The median PFS was 11.0 months. The median number of cycles received was 4.5, and 33% of patients received at least 12 cycles of selumetinib. Sixty-three percent of patients (33/52) had PFS> 6 months. Grade 4 toxicities included cardiac (1 patient), pulmonary (1), and pain (1). The most common grade 3 toxicities were gastrointestinal (13), and dermatologic (9). Thirty-four patients had sufficient DNA for mutational analysis: 6% BRAF, 41% KRAS, 15% NRAS mutations were found, and 38% had no detectable mutation. There were no statistically significant differences in the proportion of responses by any mutation.
Conclusions: Selumetinib is well tolerated and is active in the treatment of recurrent low-grade serous carcinoma. In exploratory analyses, response to selumetinib did not appear to be related to RAS/RAF mutational status, however the sample size was small. The 81% disease control rate is encouraging and worthy of further evaluation of MEK inhibitors in this population.