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

Hedy L. Kindler, Theodore G. Karrison, David R Gandara, Charles Lu, Lee M. Krug, James P. Stevenson, Pasi A. Jänne, David I. Quinn, Marianna N. Koczywas, Julie R. Brahmer, Kathy S. Albain, David A. Taber, Samuel G. Armato, Nicholas J. Vogelzang, Helen X. Chen, Walter M. Stadler, Everett E. Vokes

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139 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2509-2515
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number20
DOIs
StatePublished - Jul 10 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Kindler, H. L., Karrison, T. G., Gandara, D. R., Lu, C., Krug, L. M., Stevenson, J. P., Jänne, P. A., Quinn, D. I., Koczywas, M. N., Brahmer, J. R., Albain, K. S., Taber, D. A., Armato, S. G., Vogelzang, N. J., Chen, H. X., Stadler, W. M., & Vokes, E. E. (2012). Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. Journal of Clinical Oncology, 30(20), 2509-2515. https://doi.org/10.1200/JCO.2011.41.5869