TY - JOUR
T1 - Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma
AU - Kindler, Hedy L.
AU - Karrison, Theodore G.
AU - Gandara, David R.
AU - Lu, Charles
AU - Krug, Lee M.
AU - Stevenson, James P.
AU - Jänne, Pasi A.
AU - Quinn, David I.
AU - Koczywas, Marianna N.
AU - Brahmer, Julie R.
AU - Albain, Kathy S.
AU - Taber, David A.
AU - Armato, Samuel G.
AU - Vogelzang, Nicholas J.
AU - Chen, Helen X.
AU - Stadler, Walter M.
AU - Vokes, Everett E.
PY - 2012/7/10
Y1 - 2012/7/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2011.41.5869
DO - 10.1200/JCO.2011.41.5869
M3 - Article
C2 - 22665541
AN - SCOPUS:84864055587
SN - 0732-183X
VL - 30
SP - 2509
EP - 2515
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 20
ER -