Bevacizumab In Glioblastoma Research Articles

Role of bevacizumab therapy in the management of glioblastoma

Glioblastoma is one of the most common primary brain tumors and one of the most difficult to treat. In population-based studies only 30% of patients will survive 1 year and in the most efficacious surgery, irradiation, and chemotherapy clinical trials approximately 20% will live 2 years. Bevacizumab is a recombinant, antivascular epidermal growth factor receptor (VEGF) monoclonal antibody with 6 VEGF-binding residues that binds to VEGF, preventing VEGF from binding to its target, VEGFR-1 and VEGFR-2, on endothelial cells. Through its binding to VEGF ligands bevacizumab reduces tumor angiogenesis and vasogenic brain edema; the consequences are that bevacizumab reduces the rate of glioblastoma tumor growth and its associated tumoral edema, thereby improving quality of life and survival for patients suffering from cerebral glioblastoma. In this review, we will summarize the studies that led to the use of bevacizumab in glioblastoma and the potential side-effects and complications that can be associated with its use and, finally, new opportunities for drug combinations with bevacizumab.

Role of bevacizumab therapy in the management of glioblastoma

Role of bevacizumab therapy in the management of glioblastoma Scott J Peak, Victor A LevinNeuro-Oncology Program, Department of Neurosurgery and Neuroscience, Kaiser Permanente, Redwood City, CA, USAAbstract: Glioblastoma is one of the most common primary brain tumors and one of the most difficult to treat. In population-based studies only 30% of patients will survive 1 year and in the most efficacious surgery, irradiation, and chemotherapy clinical trials approximately 20% will live 2 years. Bevacizumab is a recombinant, antivascular epidermal growth factor receptor (VEGF) monoclonal antibody with 6 VEGF-binding residues that binds to VEGF, preventing VEGF from binding to its target, VEGFR-1 and VEGFR-2, on endothelial cells. Through its binding to VEGF ligands bevacizumab reduces tumor angiogenesis and vasogenic brain edema; the consequences are that bevacizumab reduces the rate of glioblastoma tumor growth and its associated tumoral edema, thereby improving quality of life and survival for patients suffering from cerebral glioblastoma. In this review, we will summarize the studies that led to the use of bevacizumab in glioblastoma and the potential side-effects and complications that can be associated with its use and, finally, new opportunities for drug combinations with bevacizumab.Keywords: chemotherapy, VEGF, edema, central nervous system

Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma

Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically. We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease. There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%. Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control.

Patterns of relapse and prognosis after bevacizumab (BEV) failure in recurrent glioblastoma (GBM)

2028 Background: BEV has shown promise for recurrent GBM in phase II trials. However, the patterns of relapse and prognosis of patients (pts) with GBM following BEV have not been studied systematically. This may have important implications for efficacy analysis of post-BEV therapies. Methods: We reviewed departmental databases to identify pts with recurrent GBM treated with BEV on or off clinical trials following IRB approval of this study. Pts who discontinued BEV for progressive disease (PD) were included. Records were assessed for post-BEV outcomes. Results: There were 21 pts (14 men, 7 women; median age 53 yrs, range 30–80) who discontinued BEV for PD. The median number of recurrences prior to starting BEV was 1 (range, 1–2). Patients received BEV alone (n=1) or in combination with irinotecan (n=10), hypo-fractionated re-irradiation (hyRT) (n=8), temozolomide (n=1) or temozolomide plus hyRT (n=1). The median overall survival (OS) after stopping BEV was 2.5 months (95% CI, 1.6 to 5.9); 15 patients have died. At the time BEV was discontinued, seven pts had local recurrence (initial site of disease) whereas 14 had recurred in a multifocal tumor/gliomatosis cerebri pattern. Median KPS at recurrence for those with a local pattern was 70 (range, 70–90) compared to a median of 60 (range, 40–80) in patients with a multifocal pattern (p< 0.001). Multifocal tumor/gliomatosis pattern of relapse was associated with increased risk of death (Hazard Ratio [HR]=13, 95% CI: 1.7- 101, p=0.01) compared to local relapse. KPS ≤ 60 at the time of BEV failure was also associated with increased risk of death (HR=11, 95% CI: 2.3–49, p=0.002). Additional tumor directed therapy following BEV failure was given to 11 pts (8 chemotherapy, 2 resection and chemotherapy, 1 resection). Median PFS for the therapy after BEV failure was 2.3 months (95% CI: 0.7 to 4), median OS was 4.5 months (95% CI:1.4-NR), and 6 month-PFS was 0%. Conclusions: A multifocal tumor/gliomatosis cerebri pattern of recurrence/progression is common following treatment with BEV for GBM, and is correlated with poor KPS and short survival. Treatments after BEV failure may provide only transient tumor control. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology