AACR: Selumetinib Active in Recurrent Low-grade Serous Ovarian Carcinoma

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(ChemotherapyAdvisor) – The small-molecule MEK inhibitor selumetinib was found to be active in the treatment of women with recurrent low-grade serous ovarian or peritoneal carcinoma, according to results of a Phase 2 trial presented at the AACR Annual Meeting 2012 on April 2 in Chicago.

The study, funded by the National Cancer Institute, enrolled 52 women — 58% of whom had received at least three prior chemotherapy regimens — between December 2007 and November 2009. Each received selumetinib (AZD6244, ARRY-142866) 100mg orally twice daily in four-week cycles. Median number of cycles received was 4.5; 33% of patients received at least 12 cycles of selumetinib.

BRAF, KRAS, and NRAS mutational analysis were performed, and the associations between RAS/RAF mutations and clinical outcome explored.

One patient had a complete response and 7, a partial response; 34 patients had stable disease, for a disease control rate of 80.4%. Median progression-free survival (PFS) was 11 months, with 63% of patients having a 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. No statistically significant differences in the proportion of responses by any mutation were observed.

“In exploratory analyses, response to selumetinib did not appear to be related to RAS/RAF mutational status; however, the sample size was small,” the investigators noted, adding that the disease control rate is encouraging and worthy of further evaluation of MEK inhibitors in this population.

“The results were striking,” said John Farley, MD, Creighton University School of Medicine at St. Joseph's Hospital and Medical Center in Omaha, NE, speaking on behalf the Gynecologic Oncology Group researchers who conducted the study. “Many of the patients in the study had received multiple rounds of chemotherapy and were running out of options. By using these tumors' historical inherent molecular aberrations to select patients for a treatment that in theory could exploit these abnormalities, we took an important step toward individualized cancer therapies.”


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