Similar overall survival with reduced vs. standard dose bevacizumab monotherapy in progressive glioblastoma

Cancer Med. 2020 Jan;9(2):469-475. doi: 10.1002/cam4.2616. Epub 2019 Nov 22.


Introduction: Bevacizumab has demonstrated activity in glioblastoma (GBM), but the true benefits and optimal dose-schedule are debated. A lower dose-schedule than standard-dose bevacizumab (10 mg/kg 2-weekly) might offer similar benefits with lower costs. At our Institution, patients are randomly assigned at time of primary diagnosis to Neuro-Oncologists, who have varying practices in terms of bevacizumab dose-schedule upon progression.

Methods: In a retrospective analysis we examined overall survival (OS), measured from first administered bevacizumab dose until death, according to dose-schedule. Patients with de novo WHO Grade IV GBM who received standard- or reduced-dose (5 mg/kg 2-weekly) bevacizumab were included. MGMT methylation status and time from diagnosis to bevacizumab start were examined as prognostic variables. Clinical benefit and a comparative cost analysis were assessed.

Results: In total, 1127 bevacizumab doses were administered to 118 patients [Median: 7, Range: 1-44]. Median OS (mOS) was 5.8 months. 69 (59%) patients received standard-dose bevacizumab (mOS: 5.97 months) and 49 patients received reduced-dose (mOS: 5.7 months). No statistically significant difference in OS between dosing schedule was seen (HR: 1.11, P-value: .584). Patients with MGMT methylated tumors (43%) had improved OS compared to those with unmethylated tumors; 7.03 vs 4.97 months (HR: 0.61, P-value: .027). If all patients were treated with reduced-dose bevacizumab, an estimated €2.4M cost reduction would be observed.

Conclusions: In this retrospective study, reduced-dose bevacizumab schedule resulted in similar OS to standard-dose bevacizumab monotherapy with substantial cost savings. MGMT methylation appears to convey a survival benefit in the setting of bevacizumab treatment for progressive GBM.

Keywords: MGMT; bevacizumab; cost analysis; glioblastoma; overall survival; reduced dose.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Glioblastoma / drug therapy
  • Glioblastoma / mortality*
  • Glioblastoma / pathology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate
  • Young Adult


  • Antineoplastic Agents, Alkylating
  • Bevacizumab