| General information |
| Database: | DB00625 |
| Objective: | This openlabel, prospective, multicenter singlearmphase II study combined bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) for the treatment of newly diagnosed glioblastoma (GBM). The objectives were to determine the efficacy of this treatment combination and the associated toxicity. |
| Authors: | Lai A, et al |
| Title: | Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21135282 |
| Trial Design |
| Clinical Trial Id: | NCT01013285 |
| 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 plus temozolomide during and after radiation therapy |
| Study Type: | openlabel, prospective, multicenter singlearmphase II study |
| Key Patients Feature: | Eligibilitycriteriaforthisprotocolincluded: 18yearsofage, pathologically confirmed diagnosis of intracranial GBM including gliosarcoma byWHO criteria within 6 weeks of treatment, Karnofsky performance score(KPS) 60, and adequate organ function. All patients were newly diagnosedwithout prior treatment, including polifeprosan 20 with carmustine implant(Gliadel wafer, Eisai, Woodcliff Lake, NJ). patients were required to have 200 mg of frozen tissue collected at surgery excluding most biopsy patients. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received standard RT starting within 3 to 6 weeks after surgery with concurrent administration of daily TMZ and biweekly BV. After completion of RT, patients resumed TMZ for 5 days every 4 weeks and continued biweekly BV. MGMT promoter methylation was assessed on patient tumor tissue. |
| Primary End Point: | OS |
| Secondary End Point: | PFS |
| Patients Number: | 70 |
| Trial Results |
| DLT_MTD: | No grade 5 eventsrelated to treatment were observed. Overall, treatment delivery characteristicswere similar to the EORTCNCIC trial (Appendix TableA1, online only). |
| Objective Response Rate: | The overall survival (OS) and progression free survival (PFS) were 19.6 and 13.6 months, compared to 21.1 and 7.6 months in the University of California, Los Angeles/KPLA control cohort, and 14.6 and 6.9 months in the European Organisation for Research and Treatmentof CancerNational Cancer Institute of Canada cohort |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS for the study group was 13.6 months (95% CI, 11.1 to 16.5 months) compared to 7.6 months (95% CI, 5.9 to 10.8 months) for the University of California, Los Angeles/KPLA group |
| Median OS A vs. C: | 19.6 months (95% CI, 16.1 to 23.3 months) compared to 14.6 months for the EORTCNCIC study. |
| Adverse Event(agent arm): | No grade 5 events related to treatment were observed. Overall, treatment delivery characteristics were similar to the EORTCNCIC trial. There appeared to be decreased RT interruption/ delay compared to the EORTCNCIC trial. The most common nonhematologic treatment related toxicities were fatigue, followed by venous thrombosis, hypertension (HTN), and proteinuria. |
| Conclusions: | Patients treated with BV and TMZ during and after RT showed improved PFS without improved OS compared to the University of California, Los AngelesKPLA control group. Additional studies are warranted to determine if BV administered firstline improves survival compared to BV at recurrence. |