Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma Journal Article


Authors: Kindler, H. L.; Karrison, T. G.; Gandara, D. R.; Lu, C.; Krug, L. M.; Stevenson, J. P.; Janne, P. A.; Quinn, D. I.; Koczywas, M. N.; Brahmer, J. R.; Albain, K. S.; Taber, D. A.; Armato, S. G., 3rd; Vogelzang, N. J.; Chen, H. X.; Stadler, W. M.; Vokes, E. E.
Article Title: Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma
Abstract: PURPOSE: Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM. PATIENTS AND METHODS: Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. The primary end point was progression-free survival (PFS). Patients were stratified by ECOG performance status (0 v 1) and histologic subtype (epithelial v other). Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8 every 21 days, cisplatin 75 mg/m(2) every 21 days, and bevacizumab 15 mg/kg or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression. RESULTS: One hundred fifteen patients were enrolled at 11 sites; 108 patients were evaluable. Median PFS time was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). Median overall survival (OS) times were 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91). Partial response rates were similar (24.5% for bevacizumab v 21.8% for placebo; P = .74). A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. There were no statistically significant differences in toxicity of grade 3 or greater. CONCLUSION: The addition of bevacizumab to gemcitabine/cisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM.
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 20
ISSN: 0732-183X
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 2509
End Page: 2515
Language: eng
DOI/URL:
Notes: LR: 20130712; JID: 8309333; 0 (Antibodies, Monoclonal, Humanized); 0 (Placebos); 15663-27-1 (Cisplatin); 2S9ZZM9Q9V (bevacizumab); 951-77-9 (Deoxycytidine); B76N6SBZ8R (gemcitabine); OID: NLM: PMC3397785; 2012/06/04 [aheadofprint]; ppublish