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.; Jänne, 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. © 2012 by American Society of Clinical Oncology. |
| Keywords: | vasculotropin; adult; controlled study; human tissue; treatment response; aged; disease-free survival; middle aged; major clinical study; histopathology; neutropenia; bevacizumab; cisplatin; placebo; drug dose reduction; drug withdrawal; hypertension; gemcitabine; protein blood level; progression free survival; multiple cycle treatment; peritoneal neoplasms; anemia; bleeding; randomized controlled trial; stomatitis; thrombocytopenia; antineoplastic combined chemotherapy protocols; febrile neutropenia; multicenter study; vein thrombosis; thrombosis; malignant mesothelioma; mesothelioma; phase 3 clinical trial; double blind procedure; double-blind method; deoxycytidine; alopecia; epistaxis; proteinuria; pleural neoplasms; cerebrovascular accident; placebos; perforation; antibodies, monoclonal, humanized; infection without neutropenia; visceral perforation |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 30 |
| Issue: | 20 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2012-07-10 |
| Start Page: | 2509 |
| End Page: | 2515 |
| Language: | English |
| DOI: | 10.1200/jco.2011.41.5869 |
| PROVIDER: | scopus |
| PMCID: | PMC3397785 |
| PUBMED: | 22665541 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: JCOND" - "Source: Scopus" |
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