| General information |
| Database: | DB00603 |
| Objective: | Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme. This study combined bevacizumab, a vascular endothelial growth factor inhibitor, and erlotinib, an epidermal growth factor receptor inhibitor, with standard radiation and temozolomide (TMZ), with the goal of improving overall survival (OS). |
| Authors: | Clarke JL, et al |
| Title: | A singleinstitutionphase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. |
| Journal: | Neuro Oncol. |
| Year: | 2014 |
| PMID: | 24637230 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | radiation, temozolomide, erlotinib, and bevacizumab |
| Study Type: | A singleinstitutionphase II trial |
| Key Patients Feature: | Inclusion criteria Age more than and equal to 18 y KPS more than and equal to 60 Newly diagnosed, surgically confirmed GBM or gliosarcoma, with studytreatment starting 3-5 wk after open surgery or 2-5 wk after biopsy Adequate bone marrow, liver, and kidney function |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Treatment consisted of fractionated radiotherapy to 60 Gy, with daily TMZ at 75 mg/m2/d and erlotinib 150200 mg/d (or 500600 mg/d for patients on enzymeinducing antiepileptic drugs). Bevacizumab was given at 10 mg/kg every 2 weeks, starting more than and equal to 4 weeks after surgery. After radiotherapy, adjuvant TMZ was given at 200 mg/m2/d ¡Á 5d per 28day cycle, with unchanged erlotinib and bevacizumab doses. Treatment continued until progression or for 12 months. Efficacy was compared against an institutional historical control. A sample of 55 patients was calculated to provide 85% potheyr to detect a hazard ratio of 0.67 for OS. |
| Primary End Point: | OS |
| Secondary End Point: | PFS and safety |
| Patients Number: | 59 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 13.5 months (vs 8.6 mo for HC, P = .03). |
| Median OS A vs. C: | 19.8 months (vs 18 mo for HC, P = .33) |
| Adverse Event(agent arm): | The most frequent related grade 3/4 adverse effects were lymphopenia, thrombocytopenia, neutropenia, diarrhea, weight loss, and fatigue. One patient died of disseminated aspergillosis. |
| Conclusions: | The combination of bevacizumab, erlotinib, TMZ, and radiotherapy appears to be well tolerated and improved progression free survival but did not reach the primary endpoint of improved OS. |