Study: Bevacizumab Should Not Be Withheld in Multifocal Glioblastoma

Glioblastoma has a highly infiltrative growth pattern that increases in later disease stages. Tumor cells infiltrate the brain, proliferate, and form tumor nodules at multiple locations. Glioblastoma cells secrete vascular endothelial growth factor A (VEGF-A), which induces the formation of a dysfunctional vascular system in the tumor.

Treatment with bevacizumab (Avastin or a biosimilar), which targets VEGF-A, inhibits neovascularization, and initially leads to increased tumor profusion due to improved oxygenation of the tumor tissue. However, ongoing treatment with bevacizumab leads to regression of tumor vasculature. In clinical practice, however, bevacizumab is employed cautiously in patients with multifocal glioblastomas rather than single glioblastomas because of a fear, based on unconfirmed preclinical data, that bevacizumab can increase the invasive tumor phenotype.

In order to clarify whether bevacizumab should be applied to patients with multifocal glioblastomas, the authors of a recent study, published in International Journal of Molecular Sciences, performed a retrospective data analysis of patients with glioblastomas who were treated at University Hospital Frankfurt between April 2008 and March 2016.

All patients (n = 164) with multifocal glioblastomas were compared to a matched control cohort with single glioblastomas; all patients received bevacizumab in the relapse situation. The investigators compared response rate, progression-free survival, overall survival, and relapse between the groups.

In patients with multifocal glioblastoma, a partial response (PR) was observed as best response 11 patients, stable disease (SD) in 2 patients, mixed response (MR) in 1 patient, and progressive disease (PD) in 2 patients. In the single glioblastoma cohort, PR was observed as best response in 9 patients, SD in 3 patients, MR response in 1 patient, and PD in 3 patients. No significant difference in PFS or OS was observed between the 2 groups. However, there was a trend for shorter OS in the multifocal glioblastoma group. Median PFS was 21 weeks for patients with multifocal glioblastoma, and 23.5 weeks for their matched controls. Median OS was 33 weeks in the multifocal glioblastoma group, and 43.5 weeks in the control group.

To examine whether bevacizumab led to a more infiltrative tumor phenotype, the investigators explored the share of new lesions on the patients’ last magnetic resonance imaging showing progression before the start of bevacizumab and at progression under bevacizumab therapy in both groups. There was no significant difference between the 2 groups in the frequency of new lesions.

The researchers conclude that bevacizumab should be given to patients with multifocal glioblastoma where no reasonable therapy alternative exists. “These patients often are in a critical condition and further clinical deterioration would make many patients considerably dependent on caregivers. Delaying this deterioration is of high concern both to the patients and their caregivers, even if no prolongation of survival can be achieved,” say the authors.