Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study
John Farley, William E Brady, Vinod Vathipadiekal, Heather A Lankes, Robert Coleman, Mark A Morgan, Robert Mannel, S Diane Yamada, David Mutch, William H Rodgers, Michael Birrer, David M Gershenson, John Farley, William E Brady, Vinod Vathipadiekal, Heather A Lankes, Robert Coleman, Mark A Morgan, Robert Mannel, S Diane Yamada, David Mutch, William H Rodgers, Michael Birrer, David M Gershenson
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.
Conflict of interest statement
DMG had funding provided by NCI (CTEP) and Gynecologic Oncology Group. All other co-authors have no conflicts of interest to declare.
CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.
Copyright © 2013 Elsevier Ltd. All rights reserved.
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Source: PubMed