title: Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study.
abstract: BACKGROUND
  Leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer.
  
  
  METHODS
  This was a 96-week phase III, randomized, open-label, parallel-group comparative study. All patients concomitantly received oral tamoxifen (20 mg daily). The primary endpoint was the suppression rate of serum estradiol (E2) to the menopausal level (≤30 pg/mL) from Week 4 through Week 48.
  
  
  RESULTS
  In total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E2suppression rate was 97.6 and 96.4 %, respectively. The estimated between-group difference was 1.2 % (95 % confidence interval -5.2 to 7.8). The non-inferiority of TAP-144-SR (6M) to TAP-144-SR (3M) for E2suppression was confirmed. As for safety, common adverse events were hot flush and injection site reactions including induration, pain, and erythema in both treatment groups, which were of ≤Grade 2 in severity and not serious. No significant between-group differences in safety profiles and tolerability were observed.
  
  
  CONCLUSIONS
  TAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E2. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).
authors.affiliation: Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan. kure@med.kawasaki-m.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurebayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya City University Hospital, Nagoya, Aichi, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
authors.affiliation: Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Shuuji
authors.initials: S
authors.lastname: Sumino
authors.affiliation: Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Miyajima
authors.affiliation: Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000493:pharmacokinetics; D008598:Menstruation / Q000187:drug effects; D008875:Middle Aged; D017697:Premenopause; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D013629:Tamoxifen; D004958:Estradiol; D016729:Leuprolide
keywords: Adjuvant endocrine therapy; Leuprorelin acetate 6-month depot; Luteinizing hormone–releasing hormone agonist; Ovarian function suppression; Premenopausal hormone receptor-positive breast cancer