| General information |
| Database: | DB00628 |
| Objective: | They, therefore, evaluated bevacizumab, a humanized antiVEGF monoclonal antibody, in combination with the EGFR tyrosine kinase inhibitor erlotinib, in thisphase 2 study for recurrent MG patients |
| Authors: | Sathornsumetee S, et al |
| Title: | Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy. |
| Journal: | Neuro Oncol. |
| Year: | 2010 |
| PMID: | 20716591 |
| Trial Design |
| Clinical Trial Id: | NCT00671970 |
| Agent: | bevacizumab and erlotinib
|
| Target: | NA
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | malignant glioma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab+erlotinib |
| Study Type: | openlabelphase II study |
| Key Patients Feature: | Patients with recurrent WHO grade III (anaplastic astrocytoma, oligodendroglioma, oligoastrocytoma or pleomorphic xanthoastrocytoma) or WHO grade IV MG(GBM or gliosarcoma) who met the following criteriawere eligible: age more than and equal to 18 years; more than and equal to 4 weeks from craniotomy(1 week for biopsy), prior radiotherapy, or chemotherapy (6 weeks for a nitrosourea); Karnofsky performancestatus (KPS) score more than and equal to 60; and adequate hematologic, hepatic, and renal function. Key exclusion criteriaincluded: prior therapy with bevacizumab or EGFRinhibitor; greater than 3 prior recurrences; evidence ofCNS hemorrhage; concurrent therapeutic anticoagulation; significant intercurrent illness; another primarymalignancy that required treatment within 1 year;history of myocardial infarction or stroke within 6months; or urine protein to creatinine ratio more than and equal to 1. |
| Biomarker: | hypoxiainducible factor2 alpha and VEGF receptor2 levels |
| Biomark Analysis: | Elevated hypoxiainducible factor2 alpha and VEGF receptor2 levels were associated with poor survival. |
| Control Group Info: | single arm |
| Treatment Info: | patients were stratified based on the concurrent use of enzymeinducing antiepileptic drugs (EIAEDs). Bevacizumab (10 mg/kg) was given intravenously every 2 weeks. Erlotinib was orally administered daily at 200 mg/day for patients not on EIAEDs and 500 mg/day for patients on EIAEDs. |
| Primary End Point: | 6month progression free survival (PFS6) |
| Secondary End Point: | Overall survival (OS), radiographic response, pharmacokinetics, and correlative biomarkers |
| Patients Number: | 57 |
| Trial Results |
| DLT_MTD: | Common side effects, including rash (93%), diarrhea(57%), and fatigue (66%), were mainly grade 1 or 2;however, 22 (39%) patients developed grade 3 rash. |
| Objective Response Rate: | All 32 patients were evaluated for outcome assessment.Ttheylve (48%) GBM and 10 (31%) AG patientsexperienced radiographic (complete and partial)responses (Fig. 2 and Supplementary Material, Fig.SB). |
| Disease Control Rate: | 75% in WHO grade4; 92% in WHO grade3 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 23.4 (18.1-36.1) weeks in WHO grade4; 18 (12.0-23.9) weeks in WHO grade3 |
| Median OS A vs. C: | 71.3 (44.7-123.6) weeks in WHO grade4; 44.6 (28.4-68.7) weeks in WHO grade3 |
| Adverse Event(agent arm): | Rash, mucositis, diarrhea, and fatigue were common but mostly grades 1 and 2. Among GBM patients, grade 3 rash, observed in 32%, was associated with survival benefit, whereas elevated hypoxiainducible factor2 alpha and VEGF receptor2 levels were associated with poor survival. |
| Conclusions: | Bevacizumab plus erlotinib was adequately tolerated in recurrent MG patients. Hotheyver, this regimen was associated with similar PFS benefit and radiographic response when compared with other historical bevacizumabcontaining regimens. |