Fulvestrant (Faslodex) + Anastrozole (Arimidex) vs Anastrozole
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fulvestrant; Anastrozole
Intervention description: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.; 1 mg oral Anastrozole per day during 5 years.
Intervention MeSH terms: Fulvestrant; Anastrozole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 870.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: luminal; anastrozole; fulvestrant; early breast cancer; HR+/HER2-

Summary:

      Postmenopausal women with hormone receptor positive and negative Her2 tumours.

      Before randomization, the patients will be stratified according to the center, positive nodes
      (0 vs. 1-3 vs. ≥4), previous chemotherapy (yes vs no) and hormonal receptors status.
    

Eligibility criteria:

        Inclusion criteria:

          1. Histological documentation of breast cancer.

          2. Stage I, II, IIIA and IIIC* invasive breast cancer. One of these two characteristics
             must be fulfilled:

               -  N+

               -  T > 1cm *Eligible patients T1-T3 and pN3a (patients with metastasis in
                  infraclavicular nodes would not be eligible)

          3. Local treatment with curative intention:

               -  mastectomy or tumour excision with free margins + radiotherapy

               -  axillary lymphadenectomy or sentinel node biopsy

          4. Positive hormone receptors (Estrogen Receptor [ER]+ and/or Progesterone Receptor
             [PR]+) in primary tumour tissue as measured by a central laboratory

          5. Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, defined as
             immunohistochemistry (IHC) 0 or 1+ or negative fluorescence in situ hybridization
             (FISH) (in the event of IHC 2+ or 3+)

          6. Postmenopausal women, defined as women meeting any of the following criteria:

               -  Age ≥ 60 years

               -  Age ≥ 45 years with amenorrhea ≥ 12 months in the moment of breast cancer
                  diagnosis and an intact uterus

               -  Prior bilateral ovariectomy

               -  In case previous hysterectomy, follicle stimulating hormone (FSH) and estradiol
                  levels within the postmenopausal range (using local laboratory ranges)* * In
                  patients previously treated with a luteinizing hormone releasing hormone (LH-RH)
                  analogue, the last extended release formulation should have been administered
                  more than 6 months before randomisation, and menses must not have reappeared.

          7. A World Health Organization (WHO) performance status of 0, 1, or 2.

          8. Age > 18 years

        Exclusion criteria:

          1. Presence of metastatic disease or bilateral invasive cancer

          2. ER and Progesterone Receptor (PR) negative breast cancer

          3. HER2-positive breast cancer, defined as FISH+

          4. Treatment with a non-approved or experimental drug within 4 months of randomisation

          5. Current malignancy or previous malignancy in the past 5 years (other that breast
             cancer or basal cell or squamous cell carcinoma of the skin or carcinoma in situ of
             the cervix)

          6. Pregnant or nursing patients

          7. Any of the following laboratory values within 3 months of randomisation:

               -  Platelets < 100 x 109/L

               -  Total bilirubin > 1.5 x Upper limit of reference range (ULRR)**

                  ** Patients with documented Gilbert syndrome may be included in this trial

               -  Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 2.5 x ULRR

               -  A history of:

               -  hemorrhagic diathesis (i.e. Disseminated Intravascular Coagulation [DIC],
                  coagulation factor deficiency) or

               -  long-term anticoagulant treatment (except for anti-platelet aggregants and
                  low-dose warfarin; see section 3.7)

          8. A history of hypersensitivity to the active ingredient or inactive excipients of
             fulvestrant, aromatase inhibitors, or castor oil

          9. Any concomitant severe disease advising against patient participation in the trial o
             that may jeopardize compliance with the trial protocol, such as uncontrolled heart
             disease, uncontrolled diabetes mellitus, or uncontrolled severe infections

         10. Hormone replacement therapy