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

Lancet Oncol. 2013 Feb;14(2):134-40. doi: 10.1016/S1470-2045(12)70572-7. Epub 2012 Dec 21.


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, 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Benzimidazoles / therapeutic use*
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / genetics
  • Female
  • Humans
  • MAP Kinase Signaling System
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mutation
  • Neoplasm Recurrence, Local / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics


  • AZD 6244
  • Benzimidazoles
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins

Associated data