| General information |
| Database: | DB00813 |
| Objective: | Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although singlearmphase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. they added the antiVEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, doubleblind, placebocontrolled randomizedphase II trial in patients with previously untreated, unresectable MM. |
| Authors: | Kindler HL, et al |
| Title: | Multicenter, doubleblind, placebocontrolled, randomizedphase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22665541 |
| Trial Design |
| Clinical Trial Id: | NCT00027703 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | malignant pleural mesothelioma |
| Cancer Subtype: | malignant mesothelioma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | gemcitabine/cisplatin + bevacizumab |
| Study Type: | Multicenter, doubleblind, placebocontrolled, randomizedphase II trial |
| Key Patients Feature: | Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. |
| Biomarker: | plasma VEGF concentration |
| Biomark Analysis: | A higher pretreatment plasma VEGF concentration (n = 56) was associated with shorter PFS (P = .02) and OS (P = .0066), independent of treatment arm. |
| Control Group Info: | gemcitabine/cisplatin plus placebo verus gemcitabine/cisplatin plus bevacizumab |
| Treatment Info: | 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. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 115 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). |
| Median OS A vs. C: | 15.6 and 14.7 months in the bevacizumab and placebo arms, respectively (P = .91) |
| Adverse Event(agent arm): | The rates of bleeding, thrombosis, and proteinuria were also higher in the GCB arm, but the differences were not statistically significan |
| Conclusions: | The addition of bevacizumab to gemcitabinecisplatin in this trial did not significantly improve PFS or OS in patients with advanced MM. |