Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer

Aman Buzdar, Charles Vogel, Lee Schwartzberg, August Garin, Alejandra Perez, James Ingle, Michele Houghton, Christopher Zergebel, Bill Kimball

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BACKGROUND: The objective of this study was to evaluate 3 different doses of (7α)-21-(4-[(diethylamino)methyl]-2 methoxyphenoxy)-7 methyl-19 norpregna-1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) in patients with recurrent, hormone-responsive breast cancer. METHODS: In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40 mg, 80 mg, or 120 mg to postmenopausal patients with locally advanced, or inoperable, or metastatic hormone-receptor positive breast cancer. The primary efficacy outcome was clinical benefit (CB), defined as the total number of patients who achieved a complete response, a partial response, or stable disease for ≥24 weeks. The study was a 2-stage design in which 19 patients per dose group were planned in the first stage. If at least 3 patients in any dose group achieved a CB, then that dose group was to be allowed to continue enrolling for the second stage, and the group could include up to a total of 60 patients. RESULTS: The 40-mg and 80-mg groups met the criterion and enrolled patients into the second stage. In the 40-mg group, there were 13 CB events in 60 patients (21.7%); and, in the 80-mg group, there were 12 CB events in 60 patients (20%). The 120-mg daily dose was stopped early, because it failed to achieve the criterion. For the 40-mg and 80-mg groups, the median time to progression was 15.0 weeks and 15.9 weeks, respectively. Only 1 drug-related serious adverse event (grade 3 hyperglycemia) was reported. CONCLUSIONS: TAS-108 at 40 mg and 80 mg daily demonstrated clinical activity with an encouraging duration of benefit. Because of its superior safety profile, TAS-108 40 mg daily is recommended for further development.

Original languageEnglish (US)
Pages (from-to)3244-3253
Number of pages10
JournalCancer
Volume118
Issue number13
DOIs
StatePublished - Jul 1 2012

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Breast Neoplasms
Hormones
Trientine
Double-Blind Method
Hyperglycemia
Multicenter Studies
Safety
Pharmaceutical Preparations

Keywords

  • Antiestrogen
  • Breast cancer
  • Hormone receptor positive
  • Metastatic disease
  • TAS-108

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Buzdar, A., Vogel, C., Schwartzberg, L., Garin, A., Perez, A., Ingle, J., ... Kimball, B. (2012). Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer. Cancer, 118(13), 3244-3253. https://doi.org/10.1002/cncr.26419

Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer. / Buzdar, Aman; Vogel, Charles; Schwartzberg, Lee; Garin, August; Perez, Alejandra; Ingle, James; Houghton, Michele; Zergebel, Christopher; Kimball, Bill.

In: Cancer, Vol. 118, No. 13, 01.07.2012, p. 3244-3253.

Research output: Contribution to journalArticle

Buzdar, A, Vogel, C, Schwartzberg, L, Garin, A, Perez, A, Ingle, J, Houghton, M, Zergebel, C & Kimball, B 2012, 'Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer', Cancer, vol. 118, no. 13, pp. 3244-3253. https://doi.org/10.1002/cncr.26419
Buzdar, Aman ; Vogel, Charles ; Schwartzberg, Lee ; Garin, August ; Perez, Alejandra ; Ingle, James ; Houghton, Michele ; Zergebel, Christopher ; Kimball, Bill. / Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer. In: Cancer. 2012 ; Vol. 118, No. 13. pp. 3244-3253.
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abstract = "BACKGROUND: The objective of this study was to evaluate 3 different doses of (7α)-21-(4-[(diethylamino)methyl]-2 methoxyphenoxy)-7 methyl-19 norpregna-1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) in patients with recurrent, hormone-responsive breast cancer. METHODS: In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40 mg, 80 mg, or 120 mg to postmenopausal patients with locally advanced, or inoperable, or metastatic hormone-receptor positive breast cancer. The primary efficacy outcome was clinical benefit (CB), defined as the total number of patients who achieved a complete response, a partial response, or stable disease for ≥24 weeks. The study was a 2-stage design in which 19 patients per dose group were planned in the first stage. If at least 3 patients in any dose group achieved a CB, then that dose group was to be allowed to continue enrolling for the second stage, and the group could include up to a total of 60 patients. RESULTS: The 40-mg and 80-mg groups met the criterion and enrolled patients into the second stage. In the 40-mg group, there were 13 CB events in 60 patients (21.7{\%}); and, in the 80-mg group, there were 12 CB events in 60 patients (20{\%}). The 120-mg daily dose was stopped early, because it failed to achieve the criterion. For the 40-mg and 80-mg groups, the median time to progression was 15.0 weeks and 15.9 weeks, respectively. Only 1 drug-related serious adverse event (grade 3 hyperglycemia) was reported. CONCLUSIONS: TAS-108 at 40 mg and 80 mg daily demonstrated clinical activity with an encouraging duration of benefit. Because of its superior safety profile, TAS-108 40 mg daily is recommended for further development.",
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AU - Garin, August

AU - Perez, Alejandra

AU - Ingle, James

AU - Houghton, Michele

AU - Zergebel, Christopher

AU - Kimball, Bill

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N2 - BACKGROUND: The objective of this study was to evaluate 3 different doses of (7α)-21-(4-[(diethylamino)methyl]-2 methoxyphenoxy)-7 methyl-19 norpregna-1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) in patients with recurrent, hormone-responsive breast cancer. METHODS: In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40 mg, 80 mg, or 120 mg to postmenopausal patients with locally advanced, or inoperable, or metastatic hormone-receptor positive breast cancer. The primary efficacy outcome was clinical benefit (CB), defined as the total number of patients who achieved a complete response, a partial response, or stable disease for ≥24 weeks. The study was a 2-stage design in which 19 patients per dose group were planned in the first stage. If at least 3 patients in any dose group achieved a CB, then that dose group was to be allowed to continue enrolling for the second stage, and the group could include up to a total of 60 patients. RESULTS: The 40-mg and 80-mg groups met the criterion and enrolled patients into the second stage. In the 40-mg group, there were 13 CB events in 60 patients (21.7%); and, in the 80-mg group, there were 12 CB events in 60 patients (20%). The 120-mg daily dose was stopped early, because it failed to achieve the criterion. For the 40-mg and 80-mg groups, the median time to progression was 15.0 weeks and 15.9 weeks, respectively. Only 1 drug-related serious adverse event (grade 3 hyperglycemia) was reported. CONCLUSIONS: TAS-108 at 40 mg and 80 mg daily demonstrated clinical activity with an encouraging duration of benefit. Because of its superior safety profile, TAS-108 40 mg daily is recommended for further development.

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