Conference Report

Breast Cancer Research and Treatment

, Volume 73, Issue 2, pp 161-175

Phase III Randomized Trial of Droloxifene and Tamoxifen As First-Line Endocrine Treatment of ER/PgR-Positive Advanced Breast Cancer

  • A. BuzdarAffiliated withM.D. Anderson Cancer Center, The University of Texas
  • , D. HayesAffiliated withGeorgetown University Medical Center
  • , A. El-KhoudaryAffiliated withNational Cancer Institute, Cairo University, Cairo
  • , S. YanAffiliated withCancer Hospital of the Chinese Academy of Medical Science
  • , P. LønningAffiliated withHaukeland Sykehus
  • , M. LichinitserAffiliated withCancer Research Center
  • , R. GopalAffiliated withTata Memorial Hospital
  • , G. FalksonAffiliated withUniversity of Pretoria and Pretoria Academic Hospitals
  • , K. PritchardAffiliated withToronto-Sunnybrook Regional Cancer Center
    • , A. LiptonAffiliated withM.D. Anderson Cancer Center, The University of TexasM. S. Hershey Medical Center
    • , K. WolterAffiliated withM.D. Anderson Cancer Center, The University of TexasPfizer Central Research
    • , A. LeeAffiliated withM.D. Anderson Cancer Center, The University of TexasPfizer Central Research
    • , K. FlyAffiliated withM.D. Anderson Cancer Center, The University of TexasPfizer Central Research
    • , R. ChewAffiliated withM.D. Anderson Cancer Center, The University of TexasPfizer Central Research
    • , M. AlderdiceAffiliated withM.D. Anderson Cancer Center, The University of TexasPfizer Central Research
    • , K. BurkeAffiliated withM.D. Anderson Cancer Center, The University of TexasKlinge Pharma GmbH
    • , P. EisenbergAffiliated withM.D. Anderson Cancer Center, The University of TexasSutter/CHS Cancer Research GroupFor the Droloxifene 301 Study Group

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Abstract

Purpose:This trial was designed to demonstrate equivalence between droloxifene 40 mg/d and tamoxifen 20 mg/d as first-line treatment in pre- and post-menopausal women with ER+ and/or PgR+ advanced breast cancer based on time to disease progression and tumor response.

Materials and methods:One thousand three hundred fifty four women with measurable disease, previously untreated by hormonal or chemotherapy for advanced or recurrent breast cancer, were enrolled by 179 institutions in 35 countries. Patients were stratified at baseline for menopausal status. Patients receiving adjuvant hormonal therapy within 1 year were excluded. All patients gave written informed consent, were randomized to 40 mg droloxifene or 20 mg tamoxifen daily as single-agent therapy and underwent tumor assessment every 3 months. A central committee reviewed digitized images for all cases of tumor progression or objective response.

Results:The hazard ratio (droloxifene/tamoxifen) for the primary endpoint, time to disease progression, was 1.287 favoring tamoxifen (95% C.I.: 1.114–1.487; p  <  .001). The objective response rate (CR + PR) was 22.4% for droloxifene and 28.6% for tamoxifen (p = .02). Tamoxifen was superior to droloxifene overall, among both pre- and postmenopausal patients and among patients ≤65 years; there was no difference among women ≥65 years. The hazard ratio for all-cause mortality was 0.871 (95% C.I.: 0.672–1.129; p = .29), favoring droloxifene but not statistically significant.

Conclusions:Droloxifene was significantly less effective than tamoxifen overall and particularly among women under 65 years. Tamoxifen and droloxifene were both less effective in pre-menopausal women with receptor-positive disease compared to post-menopausal women. Further clinical development of droloxifene was stopped.

advanced breast cancer droloxifene positive hormone receptors randomized trial tamoxifen