| General information |
| Database: | DB00638 |
| Objective: | Patients with non small cell lung cancer (non small cell lung cancer) and brain metastases have previously been excluded from trials of bevacizumab because of suspected risk of CNS hemorrhage. Thisphase II trial, AVF3752g (PASSPORT), specifically addressed bevacizumab safety (incidence of grade > or = 2 CNS hemorrhage) in patients with non small cell lung cancer and previously treated brain metastases. |
| Authors: | Socinski MA, et al |
| Title: | Safety of bevacizumab in patients with non small cell lung cancer and brain metastases. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19738122 |
| Trial Design |
| Clinical Trial Id: | NCT00312728 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | non-smallcell lung cancer with brain metastases |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | bevacizumab+platinumbased doublet therapy or erlotinib and secondline: bevacizumab with singleagent chemotherapy or erlotinib |
| Study Type: | openlabel, multicenter, single arm, phase II trial |
| Key Patients Feature: | Eligible patients had nonsquamous non small cell lung cancer andpreviously treated brain metastases, without evidence of progression or hemorrhage at baseline, as ascertained by clinical examination and brain imaging(magnetic resonance imaging [MRI] or computed tomography [CT]) duringthe screening period [day 7 to day 1]). Permitted prior treatment for brainmetastases included wholebrain radiation therapy (WBRT), radiosurgery (gamma knife, linear particle accelerator, or equivalent), and/or neurosurgery, provided that 3 months had elapsed since neurosurgery. patients were 18years of age, had ECOG performance status (PS) of 0 or 1, and were appropriate candidates for first or secondline systemic therapy for advanced non small cell lung cancer.The interval between completion of therapy for CNS metastases and start ofsystemic treatment was 4 weeks. however, if CNS therapy was completed 1 week but less than 4 weeks from day 1 of cycle 1, bevacizumab treatmentwas delayed until day 1 of cycle 2 |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Firstline patients received bevacizumab (15 mg/kg) every 3 weeks with platinumbased doublet therapy or erlotinib (at physician's decision), and secondline patients received bevacizumab with singleagent chemotherapy or erlotinib, until disease progression or death. |
| Treatment Info: | Firstline patients received bevacizumab (15 mg/kg) every 3 weeks with platinumbased doublet therapy or erlotinib (at physician's decision), and secondline patients received bevacizumab with singleagent chemotherapy or erlotinib, until disease progression or death. |
| Primary End Point: | incidence of symptomatic grade 2 CNS hemorrhage for bevacizumab treatment with first or secondline systemic therapy |
| Secondary End Point: | the incidence of select NCI CTCAE adverse events (AEs), and OS |
| Patients Number: | 115 |
| Trial Results |
| DLT_MTD: | There have been no(0%) reports of grade 1 to 5CNShemorrhage (95% CI, 0.0% to 3.3%) as of the data cut and to date among the 106 patients who receivedbevacizumabbased therapy A total of eight bevacizumabtargeted events occurred as of thedata cut. The only targeted grade 5 event to occur before the data cutwas a pulmonary hemorrhage |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Of the bevacizumabtargeted adverse events reported, two were grade 5. Both were pulmonary hemorrhages, one occurring during treatment and the other occurring 6 weeks after the data cut; there was also one grade 4, nonpulmonary/nonCNS hemorrhage. Twentysix patients (24.5%) discontinued study treatment as a result of an adverse event, and 37 (34.9%) discontinued because of disease progression. |
| Conclusions: | Addition of bevacizumab to various chemotherapy agents or erlotinib in patients with non small cell lung cancer and treated brain metastases seems to be safe and is associated with a low incidence of CNS hemorrhage. |