Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

J Neurooncol. 2018 Sep;139(2):383-388. doi: 10.1007/s11060-018-2873-x. Epub 2018 Apr 18.

Abstract

Background: Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting.

Methods: We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma.

Results: Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011).

Conclusions: Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

Keywords: Bevacizumab; Brain neoplasms; Glioblastoma; MGMT; Prognosis.

MeSH terms

  • Acetanilides
  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • Female
  • Follow-Up Studies
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / mortality
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Pyrroles
  • Quinolines
  • Retreatment
  • Survival Analysis
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Young Adult

Substances

  • Acetanilides
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • N-1-benzyl-2,3-dihydro-1H-pyrrolo(2,3-b)quinolin-4-yl-2-phenylacetamide
  • Pyrroles
  • Quinolines
  • Tumor Suppressor Proteins
  • Bevacizumab
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes