| General information |
| Database: | DB00594 |
| Objective: | The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM. |
| Authors: | D'Alessandris QG, et al |
| Title: | Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma. Preliminary experience. |
| Journal: | Acta Neurochir (Wien). |
| Year: | 2013 |
| PMID: | 23132371 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab and erlotinib
|
| Target: | NA
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab + erlotinib |
| Study Type: | a phase II study |
| Key Patients Feature: | They prospectively evaluated 26 adult patients (19 males and7 females, median age 52.5 years, range 29-77 years) suffering for recurrent GBM, who had previously beentreated with surgery followed by radiotherapy with concomitant and adjuvant TMZ [26]. Sixteen patients were excluded from the study due to low VEGF expression (nine cases)and abnormal phosphatase and tensin homology (PTEN)status (seven cases). Ten patients were therefore eligiblefor targeted therapy (Table 1). Four patients underwent onecraniotomy for tumor resection, five patients had one reoperation, and one patient had two reoperations.Clinical inclusion criteria were: age more than and equal to 18 years, histologicaldiagnosis of GBM, more than and equal to 4 weeks from surgery and prior radiochemotherapy, radiological evidence of recurrence or progression of disease after previous treatments, KPSmore than and equal to 70, normal liver, kidney, and bone marrow function. |
| Biomarker: | Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RTPCR, and for PTEN and VEGF expression by immunohistochemistry. |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab+erlotinib (n = 4) and bevacizumab (n = 6) |
| Treatment Info: | Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6week cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzymeinducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. |
| Primary End Point: | response rate (RR), 6month progression free survival (PFS6), and safety profile. |
| Secondary End Point: | NA |
| Patients Number: | 10 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | RR:100 % (4/4); |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.0 (3.0-31.0) months |
| Median OS A vs. C: | 9.5 (5.0-31.0) months |
| Adverse Event(agent arm): | No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation. |
| Conclusions: | To their knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient's tumor. Although they treated a limited number of patients, they obtained significantly higher RR and PFS6 than those reported in a previous trial lacking molecular tumor analysis. |