title: Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer.
abstract: BACKGROUND
  After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity.
  
  
  METHODS
  Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM.
  
  
  RESULTS
  When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating.
  
  
  CONCLUSIONS
  TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE.
  
  
  BACKGROUND
  UMIN000001841.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hozumi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D015996:Survival Rate; D017312:Toremifene / Q000627:therapeutic use*
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D017312:Toremifene; C056516:exemestane