| General information |
| Database: | DB00599 |
| Objective: | Bevacizumab is associated with decreased vascular permeability that allows for more aggressive radiotherapy schedules. they conducted a phase II trial in newly diagnosed glioblastoma utilizing a novel hypofractionated stereotactic radiotherapy (HFSRT) schedule combined with temozolomide and bevacizumab. |
| Authors: | Omuro A, et al |
| Title: | Phase II study of bevacizumab, temozolomide, and hypofractionated stereotactic radiotherapy for newly diagnosed glioblastoma. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 25107913 |
| Trial Design |
| Clinical Trial Id: | NCT01392209 |
| 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: | bevacizumab, temozolomide, and hypofractionated stereotactic radiotherapy |
| Study Type: | Phase II Study |
| Key Patients Feature: | histologically confirmed newly diagnosed glioblastoma, tumor volume 60 cc (approximately 5 cm maximum diameter), and age 18 |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with HFSRT (6 ¡Á 6 Gy to contrast enhancement and 6 ¡Á 4 Gy to FLAIR hyperintensity with dose painting) combined with concomitant/adjuvant temozolomide and bevacizumab at standard doses. |
| Primary End Point: | 1year overall survival (OS): promising = 70%; nonpromising = 50%; ¦Á = 0.1; ¦Â = 0.1. |
| Secondary End Point: | NA |
| Patients Number: | 40 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate (ORR) was 57%. Analysis of The Cancer Genome Atlas glioblastoma transcriptional subclasses (Nanostring assay) suggested patients with a proneural phenotype (26%) fared worse (ORR = 14%, vs. 77% for other subclasses; P = 0.009). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 10 months (95%CI 8-11) |
| Median OS A vs. C: | 19 months (95%CI 15-23) |
| Adverse Event(agent arm): | Treatment was generally well tolerated and followed the established toxicity profile of each drug. |
| Conclusions: | This aggressive radiotherapy schedule was safe and more convenient for patients, achieving an OS that is comparable with historical controls. Analysis of advanced neuroimaging parameters suggests ADC and FDGPET as potentially useful biomarkers, whereas tissue correlatives uncovered the poor prognosis associated with the proneural signature in nonIDH1mutated glioblastoma. |