Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma

Neurology. 2017 Apr 11;88(15):1422-1430. doi: 10.1212/WNL.0000000000003809. Epub 2017 Mar 15.

Abstract

Objective: To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles.

Methods: The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome.

Results: Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase (IDH) mutation status.

Conclusion: These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles.

Classification of evidence: This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Cohort Studies
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Female
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation / genetics
  • Sex Factors
  • Statistics, Nonparametric
  • Temozolomide
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Tumor Suppressor Proteins
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide