title: A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of California, San Francisco, California, USA.
authors.forename: Sarita
authors.initials: S
authors.lastname: Dubey
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Lee
authors.initials: L
authors.lastname: Krug
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Robin
authors.initials: R
authors.lastname: Heinze
authors.forename: Colleen
authors.initials: C
authors.lastname: Watt
authors.forename: Jeff
authors.initials: J
authors.lastname: Crawford
authors.forename: Robert
authors.initials: R
authors.lastname: Kratzke
authors.forename: Everett
authors.initials: E
authors.lastname: Vokes
authors.forename: Hedy Lee
authors.initials: HL
authors.lastname: Kindler
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010671:Phenylurea Compounds; D010766:Phosphorylation; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use*; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases