A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.
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.
Dubey
Sarita
S
University of California, San Francisco, California, USA.
Jänne
Pasi A
PA
Krug
Lee
L
Pang
Herbert
H
Wang
Xiaofei
X
Heinze
Robin
R
Watt
Colleen
C
Crawford
Jeff
J
Kratzke
Robert
R
Vokes
Everett
E
Kindler
Hedy Lee
HL
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
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases