Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.

TitleSelumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study.
Publication TypeJournal Article
Year of Publication2013
AuthorsFarley J, Brady WE, Vathipadiekal V, Lankes HA, Coleman R, Morgan MA, Mannel R, S Yamada D, Mutch D, Rodgers WH, Birrer M, Gershenson DM
JournalLancet Oncol
Volume14
Issue2
Pagination134-40
Date Published2013 Feb
ISSN1474-5488
KeywordsAdult, Aged, Benzimidazoles, Cystadenocarcinoma, Serous, Female, Humans, MAP Kinase Signaling System, Middle Aged, Mitogen-Activated Protein Kinase Kinases, Mutation, Neoplasm Recurrence, Local, Ovarian Neoplasms, Peritoneal Neoplasms, Proto-Oncogene Proteins, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), ras Proteins
Abstract

BACKGROUND: Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.

METHODS: In this open-label, single-arm phase 2 study, women (aged ≥18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint was the proportion of patients who had an objective tumour response according to RECIST version 1.1, assessed for all the treated patients. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551070.

FINDINGS: 52 patients were enrolled between Dec 17, 2007, and Nov 23, 2009. All were eligible for analyses. Eight (15%) patients had an objective response to treatment-one patient had a complete response and seven had partial responses. 34 (65%) patients had stable disease. There were no treatment-related deaths. Grade 4 toxicities were cardiac (one), pain (one), and pulmonary events (one). Grade 3 toxicities that occurred in more than one patient were gastrointestinal (13), dermatological (nine), metabolic (seven), fatigue (six), anaemia (four), pain (four), constitutional (three), and cardiac events (two).

INTERPRETATION: Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in these patients.

FUNDING: National Cancer Institute.

DOI10.1016/S1470-2045(12)70572-7
Alternate JournalLancet Oncol
PubMed ID23261356
Grant ListCA 27469 / CA / NCI NIH HHS / United States
CA 37517 / CA / NCI NIH HHS / United States
Related Faculty: 
William Rodgers, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700