This study will be a head to head comparison of letrozole versus anastrozole in the adjuvant treatment of high risk patients. Post-menopausal patients who recently have undergone their primary surgery for their breast cancer are targeted patient population. They must also have hormone positive disease and have lymph node positive disease. The primary surgery could have been a total mastectomy, lumpectomy or quadrantectomy for primary breast cancer.
Conditions
Interventions
Trade Name: Femara
Product Name: Femara
Product Code: FEM345
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: letrozole
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent. 2. Patient must be female. 3. Patient must have undergone primary breast cancer surgery with institutional standard axillary dissection such as the following: •A total mastectomy with institutional standard axillary nodal dissection. •A lumpectomy or a quadrantectomy with institutional standard axillary dissection with breast radiotherapy (may be deferred until chemotherapy is completed) in accordance with breast preservation. •Treatment of the breast cancer following diagnosis may have included any of the following: post-lumpectomy/quadrantectomy regional radiotherapy, post-mastectomy locoregional radiotherapy, postoperative chemotherapy, and trastuzumab. 4. The tumor must have been pathologic or clinical stage IIA to IIIC invasive carcinoma of the breast documented by core needle or open biopsy. Patients with Paget's disease of the nipple are eligible 5. The date of randomization must be no more than: • 12 weeks from completion of surgery or adjuvant chemotherapy • Investigators are encouraged to enroll patients as soon as possible after completion of adjuvant chemotherapy Note adjuvant radiation and endocrine therapy e.g. letrozole and anastrozole can be given at the same time as radiotherapy due to non-overlapping toxicity profile. 6. Presence of node positive disease. Positive node is defined as the presence of at least micro metastasis greater than 0.2 mm according to the AJCC Breast Staging Criteria Edition 6. 7.Patients who have had neoadjuvant chemotherapy are eligible. Positive lymph node involvement can be defined either prior to neoadjuvant chmeotherapy or at the time of surgery following their neoadjuvant therapy. Lymph node positivity is defined in the protocol 8.Presence of occult axillary lymph node(pN1-pN3b) with no evidence of primary breast tumour (T0) or only DCIS identified and whose mestastases are isolated to axillay lymph nodes associaed with the following - lymph node relects invasive adenocarcinoma histology - measurement of ER, PR and HER2 must be performed on initial lymph nodes that were biopsied - complete staging evaluation required to exclude any other primary sites of disease, including metastatic disease 9. Bilateral, synchronous breast cancer is allowed provided at least one of the primary tumours meets the eligibility criteria. 10. Hormone receptor-positive tumours, defined as any detectable estrogen or progesterone receptor expression by institutional standards. Patients who are PR positive and ER negative are eligible for the trial. Tumour slides should be submitted for central evaluation of hormone receptor status as per Section 3.5.3.3.7 and post-text Supplement 2. 11. HER2 status must be known. Note if possible tumor slides should be submitted for central confirmation of HER2 receptor status as per Section 3.5.3.3.7 and post-text Supplement 2. 12. Physical and lab exams should be obtained at time of definitive surgery to demonstrate that there is no evidence of metastatic or recurrent disease 13. Patients must have an WHO performance status of 0 or 1(0 = fully active, able to carry on all
Exclusion criteria
Exclusion criteria: 1. Presence of metastatic disease or inflammatory breast cancer as documented by dermal lymphatic invasion. 2. Presence of metachronos bilateral breast cancer. 3. Previous or concomitant other (non-breast cancer) malignancy within the previous 5 years except in situ carcinoma of the cervix or curatively treated basal and squamous cell carcinoma of the skin. 4. Presence of other non-malignant systemic diseases which may prevent prolonged follow-up. 5. Received neoadjuvant endocrine therapy 6. Hormone replacement therapy (HRT) other than Estring®, Vagifem® or low dose estrogen vaginal cream, not stopped at least 4 weeks before randomization. Thyroid replacement , insulin or other diabetic medication are permitted to be continued 7. Adjuvant anti-estrogen therapy for more than 1 month immediately following surgery, radiotherapy and/or chemotherapy. 8. Breast cancer chemoprevention with anti-estrogens if less than 18 months between stopping and diagnosis of breast cancer. 9. Severe hepatic dysfunction defined as Child-Pugh grade C. 10. Therapy with any hormonal agent such as raloxifene for management of osteoporosis. (Patients are eligible only if these medications are discontinued 4 weeks prior to randomization).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the rate of disease free survival (DFS) at 5 years in postmenopausal women with hormone receptor and lymph node positive breast cancer randomized between letrozole and anastrozole.; Secondary Objective: • To compare the general safety between the two treatment arms. • To compare the two treatment groups in a descriptive manner with the other indicators of efficacy including overall survival, time to development of distant metastases,time to development of contra lateral breast cancer and distant disease free survival. • Compare the effect of treatment on serum lipid profiles between treatment arms, and describe the incidence of cardiovascular events in each treatment arm • Describe the incidence of bone fractures in each treatment arm •Describe the relationship between central pathology review vs local pathology review of oestrogen and progesterone hormone receptor levels and HER2 status See Amdt 3 for new added secondary objectives ; Primary end point(s): Disease Free Survival | — |
Countries
Austria, Belgium, Denmark, Finland, Germany, Ireland, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed