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Relation between bevacizumab dose intensity and high-grade glioma survival: a retrospective study in two large cohorts

  • Clinical Study - Patient Study
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Abstract

Bevacizumab is one of the rare drugs that could improve high-grade glioma outcome after failure of chemoradiotherapy. However, to date, there is no biomarker predictive for efficacy of bevacizumab therapy in terms of survival improvement for patients with high-grade glioma. We performed a retrospective analysis of clinical factors associated with patient survival using a training cohort of 110 consecutive patients treated with bevacizumab for recurrent high-grade glioma and an independent validation cohort of 109 patients. In the training cohort, 110 consecutive patients received bevacizumab-based therapy. The number of chemotherapy cycles delivered was 1,411. Median follow-up was 12 months. Thirty-four patients (31%) had objective partial response and 24% had stable disease on magnetic resonance imaging evaluation. Median progression-free survival (PFS) and overall survival (OS) were 4.3 and 9.2 months, respectively. On univariate analysis, among classical prognosis factors, only Karnofsky status ≥70% was associated with improved outcome. Surprisingly, patients with low bevacizumab dose intensity (<5 mg/kg/week) had better PFS (12 vs. 2 months, P < 0.0001) and OS (16 vs. 6 months, P = 0.0002). On multivariate analysis, low bevacizumab dose intensity was the most significant independent prognostic factor of survival. Analysis of the validation cohort yielded similar results, externally validating this observation. This large retrospective study using two independent cohorts of high-grade glioma suggests that the currently recommended dosage of bevacizumab (5 mg/kg/week) is not optimal. Further prospective randomized trials using lower dosages are warranted.

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Authors and Affiliations

  1. Department of Medical Oncology, Georges Francois Leclerc Cancer Center, 1 rue du professeur Marion, Dijon, 21000, France

    Veronique Lorgis, Geric Maura, Sylvain Ladoire & François Ghiringhelli

  2. Neuro-Oncology Unit, Department of Neurology, University Hospital Nancy, Nancy, France

    Guillaume Coppa, Kahina Hassani & Luc Taillandier

  3. Department of Medical Oncology, University Hospital Amiens, Amiens, France

    Bruno Chauffert

  4. University of Burgundy, Faculty of Medicine, Dijon, France

    Lionel Apetoh, Sylvain Ladoire & François Ghiringhelli

  5. INSERM AVENIR Team UMR866, Faculty of Medicine, Dijon, France

    Lionel Apetoh, Sylvain Ladoire & François Ghiringhelli

  6. Department of Pharmacy, University Hospital, Nancy, France

    Guillaume Coppa & Kahina Hassani

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  1. Veronique Lorgis
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  2. Geric Maura
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  3. Guillaume Coppa
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  4. Kahina Hassani
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Correspondence to Sylvain Ladoire or François Ghiringhelli.

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V. Lorgis, G. Maura, S. Ladoire, and F. Ghiringhelli share coauthorship.

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Lorgis, V., Maura, G., Coppa, G. et al. Relation between bevacizumab dose intensity and high-grade glioma survival: a retrospective study in two large cohorts. J Neurooncol 107, 351–358 (2012). https://doi.org/10.1007/s11060-011-0748-5

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  • DOI: https://doi.org/10.1007/s11060-011-0748-5

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