Imatinib mesylate (Gleevec®) in advanced breast cancer-expressing C-Kit or PDGFR-β: Clinical activity and biological correlations

M. Cristofanilli*, P. Morandi, S. Krishnamurthy, J. M. Reuben, B. N. Lee, D. Francis, D. J. Booser, M. C. Green, B. K. Arun, L. Pusztai, A. Lopez, R. Islam, V. Valero, G. N. Hortobagyi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Background: Novel molecular therapies for metastatic breast cancer (MBC) are necessary to improve the dismal prognosis of this condition. Imatinib mesylate (Gleevec®) inhibits several protein tyrosine kinases, including platelet-derived growth factor receptor (PDGFR) and c-kit, which are preferentially expressed in tumor cells. We tested the activity of imatinib mesylate in MBC with overexpression of PDGFR or c-kit. Additionally, we sought to determine the biological correlates and immunomodulatory effects. Patients and methods: Thirteen patients were treated with Imatinib administered orally at 400 mg p.o. b.i.d. (800 mg/day), until disease progression. All patients demonstrated PDGFR-β overexpression and none showed c-kit expression. Results: No objective responses were observed among the 13 patients treated in an intention-to-treat analysis. All patients experienced disease progression, with a median time to progression of 1.2 months. Twelve patients have died, and the median overall survival was 7.7 months. No patient had a serious adverse event. Imatinib therapy had no effect on the plasma levels of the angiogenesis-related cytokines, vascular endothelial growth factor, PDGF, b-fibroblast growth factor, and E-selectin. Immune studies showed imatinib inhibits interferon-γ production by TCR-activated CD4+ T cells. Conclusion: Imatinib as a single agent has no clinical activity in PDGFR-overexpressing MBC and has potential immunosuppressive effects.

Original languageEnglish (US)
Pages (from-to)1713-1719
Number of pages7
JournalAnnals of Oncology
Volume19
Issue number10
DOIs
StatePublished - 2008

Keywords

  • Imatinib
  • Immune-suppression
  • Metastatic breast cancer
  • c-kit expression

ASJC Scopus subject areas

  • Hematology
  • Oncology

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