Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant in hormone receptor-positive metastatic breast cancer: New York Cancer Consortium Trial P6205

T. Li, P. J. Christos, J. A. Sparano, D. L. Hershman, S. Hoschander, K. O'Brien, J. J. Wright, L. T. Vahdat

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: Fulvestrant produces a clinical benefit rate (CBR) of ∼45% in tamoxifen-resistant, hormone receptor (HR)-positive metastatic breast cancer (MBC) and 32% in aromatase inhibitor (AI)-resistant disease. The farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has preclinical and clinical activity in endocrine therapy-resistant disease. The objective of this study was to determine the efficacy and safety of tipifarnib-fulvestrant combination in HR-positive MBC. Patients and methods: Postmenopausal women with no prior chemotherapy for metastatic disease received i.m. fulvestrant 250 mg on day 1 plus oral tipifarnib 300 mg twice daily on days 1-21 every 28 days. The primary end point was CBR. Results: The CBR was 51.6% [95% confidence interval (CI) 34.0% to 69.2%] in 31 eligible patients and 47.6% (95% CI 26.3% to 69.0%) in 21 patients with AI-resistant disease. A futility analysis indicated that it was unlikely to achieve the prespecified 70% CBR. Tipifarnib dose modification was required in 8 of 33 treated patients (24%). Conclusions: The target CBR of 70% for the tipifarnib-fulvestrant combination in HR-positive MBC was set too high and was not achieved. The 48% CBR in AI-resistant disease compares favorably with the 32% CBR observed with fulvestrant alone in prior studies and merit further clinical and translational evaluation.

Original languageEnglish (US)
Pages (from-to)642-647
Number of pages6
JournalAnnals of Oncology
Volume20
Issue number4
DOIs
StatePublished - Apr 7 2009

Keywords

  • Farnesyl transferase inhibitor
  • Fulvestrant
  • Metastatic breast cancer
  • Postmenopausal
  • Selective estrogen receptor downregulator
  • Tipifarnib

ASJC Scopus subject areas

  • Hematology
  • Oncology

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