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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 - 2009

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tipifarnib
Farnesyltranstransferase
Aromatase Inhibitors
Hormones
Breast Neoplasms
Neoplasms
Confidence Intervals
Medical Futility
Tamoxifen
fulvestrant
Safety
Drug Therapy

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant in hormone receptor-positive metastatic breast cancer : New York Cancer Consortium Trial P6205. / Li, T.; Christos, P. J.; Sparano, Joseph A.; Hershman, D. L.; Hoschander, S.; O'Brien, K.; Wright, J. J.; Vahdat, L. T.

In: Annals of Oncology, Vol. 20, No. 4, 2009, p. 642-647.

Research output: Contribution to journalArticle

Li, T. ; Christos, P. J. ; Sparano, Joseph A. ; Hershman, D. L. ; Hoschander, S. ; O'Brien, K. ; Wright, J. J. ; Vahdat, L. T. / Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant in hormone receptor-positive metastatic breast cancer : New York Cancer Consortium Trial P6205. In: Annals of Oncology. 2009 ; Vol. 20, No. 4. pp. 642-647.
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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.",
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T1 - Phase II trial of the farnesyltransferase inhibitor tipifarnib plus fulvestrant in hormone receptor-positive metastatic breast cancer

T2 - New York Cancer Consortium Trial P6205

AU - Li, T.

AU - Christos, P. J.

AU - Sparano, Joseph A.

AU - Hershman, D. L.

AU - Hoschander, S.

AU - O'Brien, K.

AU - Wright, J. J.

AU - Vahdat, L. T.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Farnesyl transferase inhibitor

KW - Fulvestrant

KW - Metastatic breast cancer

KW - Postmenopausal

KW - Selective estrogen receptor downregulator

KW - Tipifarnib

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DO - 10.1093/annonc/mdn689

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JF - Annals of Oncology

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