An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma

Norden, Andrew D.; Drappatz, Jan; Muzikansky, Alona; David, Karly; Gerard, Mary; McNamara, Mairéad; Phan, P.; Ross, Ainsley; Kesari, Santosh; Wen, Patrick Y.

doi:10.1007/s11060-008-9745-8

Cited by 130 publications

(85 citation statements)

References 18 publications

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“…However, upon recurrence, tumors treated with antiangiogenic therapies display an increasingly invasive phenotype [11,17,[26][27][28]. Given this phenotypic alteration observed in human patients, tumor borders following treatment of GL261 gliomas with aflibercept were analyzed.…”

Section: Antiangiogenic Therapy Results In Both Proangiogenic and Promentioning

confidence: 99%

“…While bevacizumab is the first antiangiogenic therapy approved for the treatment of recurrent GBM, results in clinical trials have been mixed [10]. Phase II clinical trials utilizing bevacizumab for the treatment of recurrent gliomas have demonstrated marked improvements in progression-free survival, although overall survival is only marginally, if at all, affected [11][12][13]. A more recent phase II trial investigating the effects of bevacizumab on recurrent anaplastic gliomas reported improvement in disease symptoms and increased tumor responsiveness, despite seeing no significant change in progression-free survival or overall survival [14].…”

Section: Introductionmentioning

confidence: 99%

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Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

et al. 2016

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The addition of antiangiogenic therapy to the standard-of-care treatment regimen for recurring glioblastoma has provided some clinical benefits while also delineating numerous caveats, prompting evaluation of the elicited alterations to the tumor microenvironment. Of critical importance, given the steadily increasing incorporation of immunotherapeutic approaches clinically, is an enhanced understanding of the interplay between angiogenic and immune response pathways within tumors. In the present study, the GL261 glioma mouse model was used to determine the effects of antiangiogenic treatment in an immune-competent host. Following weekly systemic administration of aflibercept, an inhibitor of vascular endothelial growth factor, tumor volume was assessed by magnetic resonance imaging and changes to the tumor microenvironment were determined. Treatment with aflibercept resulted in reduced tumor burden and increased survival compared with controls. Additionally, decreased vascular permeability and preservation of the integrity of tight junction proteins were observed. Treated tumors also displayed hallmarks of anti-angiogenic evasion, including marked upregulation of vascular endothelial growth factor expression and increased tumor invasiveness. Aflibercept was then administered in combination with a picornavirusbased antitumor vaccine and tumor progression was evaluated. This combination therapy significantly delayed tumor progression and extended survival beyond that observed for either therapy alone. As such, this work demonstrates the efficacy of combined antiangiogenic and immunotherapy approaches for treating established gliomas and provides a foundation for further evaluation of the effects of antiangiogenic therapy in the context of endogenous or vaccine-induced inflammatory responses.

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Section: Antiangiogenic Therapy Results In Both Proangiogenic and Promentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

et al. 2016

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“…The makeup of the current as well as novel revised response criteria do not allow to easily differentiate this effect on the barrier permeability from a direct antitumor effect [9,10]. So far, the unprecedented high response rates these agents produced in recurrent glioblastoma have not translated into a survival benefit of the same magnitude [11].…”

Section: Introductionmentioning

confidence: 99%

“…For BEV, various patient series have suggested an increase in diffusely or distantly recurring tumors [11,19]. This gliomatosis-like phenotype or remote spread is best depicted on fluid-attenuated inversion recovery (FLAIR) MRI sequences [11].…”

Section: Introductionmentioning

confidence: 99%

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Patterns of Progression in Malignant Glioma Following Anti-VEGF Therapy: Perceptions and Evidence

Wick

Weiler

et al. 2011

Curr Neurol Neurosci Rep

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Antiangiogenic treatment has recently become an integral part of modern cancer therapy targeting the vasculature of numerous aggressive malignancies including glioblastoma. There is preclinical evidence that antiangiogenic therapies promote glioma cell invasiveness. In clinical series, upon progression on antiangiogenic therapy with the vascular endothelial growth factor-directed antibody bevacizumab (BEV), glioblastoma has been reported to display a more infiltrative pattern of recurrence. This distant spread at recurrence or progression and a gliomatosis cerebri-like growth pattern is best detectable on fluid-attenuated inversion recovery MRI. The frequency of up to 20% to 30% of such a pattern in BEV-treated patients is higher than expected to occur without BEV. Older reports and common clinical knowledge estimate the frequency of diffuse or distant spread in recurrent glioblastoma at 10%. This observation stimulated two streams of research. One is to overcome this often insidious adverse effect of antiangiogenic treatment, to optimize antiangiogenic therapies and to face this major challenge, integrating antiangiogenic with anti-invasive mechanisms into one combined treatment concept. The second is questioning a specific property of antiangiogenic therapy to induce diffuse or distant spread. Here, alternative hypotheses of increased awareness and better imaging as well as invasiveness being part of the natural course of the disease have been tested. Without doubt, migration and invasiveness are major obstacles to successful glioma therapy, notably local therapies, both in the natural course of the disease and in the concept of "evasive resistance." However, clinical analyses of case series, matched pairs analyses, and follow-up on the BRAIN trial (A Study to Evaluate Bevacizumab Alone or in Combination with Irinotecan for Treatment of Glioblastoma Multiforme), which led to accelerated approval of BEV for recurrent glioblastoma in the United States, have not supported a specific propensity of BEV to induce diffuse growth or distant spread at recurrence.

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Bevacizumab for Malignant Gliomas

Iwamoto¹,

Fine²

2010

Arch Neurol

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alignant gliomas are the most common and aggressive primary brain tumors in adults. Despite optimal treatment with surgery, radiotherapy, and temozolomide, tumor recurrences are frequent and patients with malignant gliomas continue to have poor prognoses. Malignant gliomas are often highly vascularized, and significant advances have been made in the last few decades in our understanding of the mechanisms of tumor angiogenesis. Recently, bevacizumab, an antibody against vascular endothelial growth factor, has demonstrated significant activity in recurrent glioblastomas, resulting in US Food and Drug Administration approval and raising the prospect for other antiangiogenic drugs now entering clinical trials.

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An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma

Cited by 130 publications

References 18 publications

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

Patterns of Progression in Malignant Glioma Following Anti-VEGF Therapy: Perceptions and Evidence

Bevacizumab for Malignant Gliomas

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