| General information |
| Database: | DB00606 |
| Objective: | In a randomizedphase II study, they investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (BevIri) versus bevacizumab combined with temozolomide (BevTem) before, during and after radiotherapy in newly diagnosed GBM. |
| Authors: | Hofland KF, et al |
| Title: | Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomizedphase II study. |
| Journal: | Acta Oncol. |
| Year: | 2014 |
| PMID: | 24456504 |
| Trial Design |
| Clinical Trial Id: | NCT00817284 |
| 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: | Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy |
| Study Type: | A randomizedphase II study |
| Key Patients Feature: | Histological verified GBM; residual contrast enhancing tumor 1 cm on the baseline MR scan (done 14 days prior to therapy); informed consent; noprior therapy for GBM except resection or biopsy;performance status 2; age 18 years; platelets, hemoglobin, leukocytes and neutrophile granulocyteswithin normal limits, liver transaminases 3 uppernormal limit (UNL), bilirubin 1.5 ULN, secreatinin 1.5 UNL or a glomerular filtration rate 60ml/min by CrEDTA clearance, activated partialthromboplastin time and international normalizedratio UNL; use of oral contraceptives or IUD byfertile females and use of condom by fertile males;no cerebral bleeding on baseline MR scan. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab and irinotecan versus bevacizumab and temozolomide |
| Treatment Info: | After surgery, patients were randomized to BevIri or BevTem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant BevIri or BevTem followed by adjuvant BevIri or BevTem for another eight weeks. BevIri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. BevTem: Bevacizumab was given as in BevIri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. |
| Primary End Point: | response after neoadjuvant chemotherapy and a prespecified response rate of 30% or more |
| Secondary End Point: | progression free survival (PFS) and toxicity. |
| Patients Number: | 63 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The response rate was 32% (95% CI 1751%) for BevTem (n = 32) and 23% (95% CI 944%) for BevIri (n = 31) (p = 0.56). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.7 and 7.3 months for BevTem and BevIri, respectively. |
| Median OS A vs. C: | The median survival in the full perprotocol population (n 63) was 13.8 months (95% CI 12.4-15.3 months). The median survival was 15.1 months in the BevIri arm (95% CI 9.6-20.6 months) and 11.8 months in the BevTem arm (95% CI 8.2-15.3 months). |
| Adverse Event(agent arm): | Hematological toxicity was more frequent with BevTem including one death from febrile neutropenia whereas nonhematological toxicity was manageable. |
| Conclusions: | Only the BevTem arm met the prespecified level of activity of interest. Our results did not indicate any benefit from BevIri in firstline therapy as opposed to BevTem in terms of response and PFS. |