Abstract
Abstract
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.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr CT-05. doi:1538-7445.AM2012-CT-05