Hypertension and proteinuria as clinical biomarkers of response to bevacizumab in glioblastoma patients

J Neurooncol. 2020 Mar;147(1):109-116. doi: 10.1007/s11060-020-03404-z. Epub 2020 Jan 23.

Abstract

Introduction: Arterial hypertension and proteinuria are common side effects of antiangiogenic treatment and might represent a biomarker of response in patients with glioblastoma. The aim of this study was to assess the impact of these side effects in predicting therapeutic response to second line chemotherapy with bevacizumab.

Methods: We evaluated clinical and survival data of glioblastoma patients who underwent treatment with bevacizumab after progression under temozolomide, at CHUSJ between 2010 and 2017. We analysed treatment-related arterial hypertension, proteinuria grade, thrombotic and haemorrhagic events during treatment. Overall survival (OS) and progression free survival (PFS) under bevacizumab were calculated according to the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards method.

Results: We evaluated 140 patients. Arterial hypertension and proteinuria occurred in 23 (16.3%) and 17 (12.1%) patients, respectively. PFS during treatment with bevacizumab was 12 months (95% CI 7.9-16.1) in the hypertensive group and 4 months (95% CI 3.2-4.8) in the normotensive group (p = 0.005). Patients with proteinuria had a PFS of 10 months (95% CI 4.9-15.0) versus 4 months (95% CI 3.4-4.8) in patients without proteinuria (p = 0.002). Multivariate analysis revealed hypertension and proteinuria as independent prognostic factors of PFS and OS.

Conclusion: Our data suggest that hypertension and proteinuria can be effective predictors of response to antiangiogenic therapy in recurrent glioblastoma and are associated with longer disease control.

Keywords: Bevacizumab; Glioblastoma; Hypertension; Predictors; Progression-free survival; Proteinuria.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / adverse effects*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects*
  • Bevacizumab / therapeutic use*
  • Biomarkers, Tumor
  • Brain Neoplasms / drug therapy*
  • Female
  • Glioblastoma / drug therapy*
  • Humans
  • Hypertension / chemically induced*
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Proteinuria / chemically induced*
  • Retrospective Studies
  • Temozolomide

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Bevacizumab
  • Temozolomide