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

Research output: Contribution to journalArticlepeer-review

72 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

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

ASJC Scopus subject areas

  • Hematology
  • Oncology

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