A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients

J. J. Raizer*, P. Giglio, J. Hu, M. Groves, R. Merrell, C. Conrad, S. Phuphanich, V. K. Puduvalli, M. Loghin, N. Paleologos, Y. Yuan, D. Liu, A. Rademaker, W. K. Yung, B. Vaillant, J. Rudnick, M. Chamberlain, N. Vick, S. Grimm, I. W. Tremont-LukatsJ. De Groot, K. Aldape, M. R. Gilbert

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Survival for glioblastoma (GBM) patients with an unmethyated MGMT promoter in their tumor is generally worse than methylated MGMT tumors, as temozolomide (TMZ) response is limited. How to better treat patients with unmethylated MGMT is unknown. We performed a trial combining erlotinib and bevacizumab in unmethylated GBM patients after completion of radiation (RT) and TMZ. GBM patients with an unmethylated MGMT promoter were trial eligible. Patient received standard RT (60 Gy) and TMZ (75 mg/m2 × 6 weeks) after surgical resection of their tumor. After completion of RT they started erlotinib 150 mg daily and bevacizumab 10 mg/kg every 2 weeks until progression. Imaging evaluations occurred every 8 weeks. The primary endpoint was overall survival. Of the 48 unmethylated patients enrolled, 46 were evaluable (29 men and 17 women); median age was 55.5 years (29–75) and median KPS was 90 (70–100). All patients completed RT with TMZ. The median number of cycles (1 cycle was 4 weeks) was 8 (2–47). Forty-one patients either progressed or died with a median progression free survival of 9.2 months. At a follow up of 33 months the median overall survival was 13.2 months. There were no unexpected toxicities and most observed toxicities were categorized as CTC grade 1 or 2. The combination of erlotinib and bevacizumab is tolerable but did not meet our primary endpoint of increasing survival. Importantly, more trials are needed to find better therapies for GBM patients with an unmethylated MGMT promoter.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalJournal of Neuro-Oncology
Volume126
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Bevacizumab
  • Erlotinib
  • Glioblastoma
  • MGMT

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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