A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.

Published

Journal Article

Malignant mesotheliomas (MMs) express vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and cKIT. Sorafenib is a potent inhibitor of the ras/raf/MEK pathway and also targets VEGFR and cKIT. We evaluated the activity of sorafenib in patients with unresectable mesothelioma.MM patients who had received 0 to 1 prior chemotherapy regimens were treated with sorafenib 400 mg orally twice daily continuously. The primary end point was objective response. ERK1/2 phosphorylation in archival tissues was correlated with response and survival.A total of 51 patients were enrolled, 50 were evaluable and included in the analysis. Three patients had a partial response (6% [95% confidence interval = 1.3-16.6%]), and 27 (54% [95% confidence interval = 39.3-68.2%]) had stable disease. Median progression-free survival and median overall survival (OS) were 3.6 and 9.7 months, respectively. Median survival was superior in epithelioid histology versus other types (10.7 versus 3.7 months, p = 0.0179). The difference in median OS between pretreated and chemonaive patients was not statistically significant (13.2 versus 5 months, p = 0.3117). Low/negative baseline tumor phospho-ERK1/2 levels were associated with improved OS (13.9 versus 5.2 months, p = 0.0066).Sorafenib has limited activity in advanced MM patients, similar to that seen with other VEGFR tyrosine kinase inhibitors. Additional studies of sorafenib in MM are not warranted.

Full Text

Duke Authors

Cited Authors

  • Dubey, S; Jänne, PA; Krug, L; Pang, H; Wang, X; Heinze, R; Watt, C; Crawford, J; Kratzke, R; Vokes, E; Kindler, HL

Published Date

  • October 2010

Published In

Volume / Issue

  • 5 / 10

Start / End Page

  • 1655 - 1661

PubMed ID

  • 20736856

Pubmed Central ID

  • 20736856

Electronic International Standard Serial Number (EISSN)

  • 1556-1380

International Standard Serial Number (ISSN)

  • 1556-0864

Digital Object Identifier (DOI)

  • 10.1097/JTO.0b013e3181ec18db

Language

  • eng