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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U2 - 10.1093/annonc/mdn689

DO - 10.1093/annonc/mdn689

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JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

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