Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma

Jennie W. Taylor, Jorg Dietrich, Elizabeth R. Gerstner, Andrew D. Norden, Mikael L. Rinne, Daniel P. Cahill, Anat Stemmer-Rachamimov, Patrick Y. Wen, Rebecca A. Betensky, Diana H. Giorgio, Kellis Snodgrass, Alison E. Randall, Tracy T. Batchelor, Andrew S. Chi

Research output: Contribution to journalArticle

Abstract

Tumor cell infiltration is a major mechanism of treatment escape in glioblastoma. Src is an intracellular tyrosine kinase that mediates tumor cell motility and invasiveness. We evaluated the efficacy and safety of bosutinib, a tyrosine kinase inhibitor that potently inhibits Src and Abl, in patients with recurrent glioblastoma. In this two-arm study, patients with histologically confirmed recurrent glioblastoma and ≤2 relapses, not previously treated with anti-vascular endothelial growth factor (VEGF) therapy, were administered oral bosutinib 400 mg daily. Arm A planned for 6 patients who were candidates for surgical resection to be given bosutinib for 7–9 days prior to resection. Arm B was a two-stage design phase 2 trial targeting 30 patients. The primary endpoint was progression-free survival at 6 months (PFS6) in Arm B. After 9 patients enrolled onto stage 1 of Arm B, 9 (100 %) patients progressed within 6 months. Therefore, the study met the pre-specified criteria for early closure and both Arms were closed. In Arm B, Median PFS was 7.71 weeks and median OS was 50 weeks. Best objective response was stable disease in one patient (11.1 %). Seven patients (77.8 %) had treatment-related AEs of any grade and 2 (22.2 %) were grade ≥3. Arm A was closed after 2 patients enrolled. Src activation was evident in all archival tumor samples. Bosutinib monotherapy does not appear to be effective in recurrent glioblastoma. However, Src remains a potential target based on its upregulation in tumor samples and role in glioma invasion.

Original languageEnglish (US)
Pages (from-to)557-563
Number of pages7
JournalJournal of Neuro-Oncology
Volume121
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Bosutinib
  • Glioblastoma
  • Invasion
  • Src inhibitor

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase 2 study of bosutinib, a Src inhibitor, in adults with recurrent glioblastoma'. Together they form a unique fingerprint.

Cite this