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

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• 作者：Prof John Farley ; MD^a ; ^{John.farley@chw.edu} ; William E Brady ; PhD^b ; Vinod Vathipadiekal ; PhD^c ; Heather A Lankes ; PhD^b ; Prof Robert Coleman ; MD^d ; Prof Mark A Morgan ; MD^e ; Prof Robert Mannel ; MD^f ; Prof S Diane Yamada ; MD^g ; Prof David Mutch ; MD^h ; Prof William H Rodgers ; MDⁱ ; Michael Birrer ; MD^c ; David M Gershenson ; MD^d
• 刊名：Lancet Oncology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：14
• 期：2
• 页码：134-140
• 全文大小：148 K

文摘

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Summary

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 ¡Ý18 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 , number .

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¡ªone 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.