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).Methods
Treatment consisted of fractionated radiotherapy to 60 Gy, with daily TMZ at 75 mg/m2/d and erlotinib 150–200 mg/d (or 500–600 mg/d for patients on enzyme-inducing antiepileptic drugs). Bevacizumab was given at 10 mg/kg every 2 weeks, starting ≥4 weeks after surgery. After radiotherapy, adjuvant TMZ was given at 200 mg/m2/d × 5d per 28-day 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% power to detect a hazard ratio of 0.67 for OS.Results
Fifty-nine patients were enrolled for efficacy analysis after a 15-patient safety lead-in. For the efficacy group, median age was 54 years; median KPS was 90. Gross total and subtotal resections were achieved in 33% and 53%, respectively. The most frequent related grade 3/4 adverse effects were lymphopenia, thrombocytopenia, neutropenia, diarrhea, weight loss, and fatigue. One patient died of disseminated aspergillosis. Median OS was 19.8 months (vs 18 mo for HC, P = .33) and median progression-free survival was 13.5 months (vs 8.6 mo for HC, P = .03).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.