Rechallenging Recurrent Glioblastoma with Intra-Arterial Bevacizumab with Blood Brain-Barrier Disruption Results in Radiographic Response

World Neurosurg. 2019 Nov:131:234-241. doi: 10.1016/j.wneu.2019.07.137. Epub 2019 Jul 24.

Abstract

Background: High-dose bevacizumab delivered via super selective intra-arterial cerebral infusion (SIACI) is one promising clinical trial combination for patients with glioblastoma (GBM). Although both continuous intravenous and intra-arterial administration of bevacizumab, and rechallenge with intravenous bevacizumab, have demonstrated improved survival, this is the first description of rechallenging GBM with SIACI of bevacizumab.

Case description: We report a case of a 43-year-old woman with recurrent GBM who had received treatment from 3 clinical trials, including a rechallenge with SIACI of bevacizumab. First, she enrolled into a phase I/II trial for patients newly diagnosed with GBM (NCT01811498) and received 3 doses of SIACI bevacizumab over 180 days in addition to standard of care chemotherapy and radiation. Following progression, as indicated on her magnetic resonance imaging scan, she consented for a separate clinical trial for her disease and received 2 cycles of temozolomide with an investigational agent. The patient was removed from the study on tumor progression. Subsequently, she was rechallenged with SIACI of bevacizumab via a third clinical trial (NCT01269853) and then completed 3 intravenous infusions. After completing the third trial, her magnetic resonance imaging scan demonstrated improvement based on Response Assessment In Neuro-Oncology criteria.

Conclusions: This is the first report to highlight the effect of rechallenging a patient with SIACI of bevacizumab following disease progression after initial bevacizumab treatment and subsequent alternate clinical trial failure. There is a need to conduct further clinical trials to evaluate the benefits of rechallenge with SIACI versus intravenous bevacizumab for GBM and further explore theories of bevacizumab resistance.

Keywords: Bevacizumab; Blood–brain barrier disruption; Glioblastoma; Intra-arterial; Recurrent GBM; Vascular endothelial growth factor.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Bevacizumab / administration & dosage*
  • Blood-Brain Barrier / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / surgery
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Drugs, Investigational / administration & dosage
  • Fatal Outcome
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / radiotherapy
  • Glioblastoma / surgery
  • Humans
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Magnetic Resonance Imaging
  • Neoplasm Recurrence, Local / drug therapy*
  • Retreatment / methods
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Drugs, Investigational
  • Bevacizumab