Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using drugs such as anastrozole and fulvestrant may fight breast cancer by blocking the use of estrogen. It is not yet known whether anastrozole is more effective with or without fulvestrant in treating breast cancer. PURPOSE: This randomized phase III trial is studying giving anastrozole together with fulvestrant to see how well it works compared to anastrozole alone as first-line therapy in treating postmenopausal women with metastatic breast cancer.
Detailed description
OBJECTIVES: * Compare the time to tumor progression in postmenopausal women with metastatic breast cancer treated with anastrozole with or without fulvestrant as first-line therapy. * Compare the clinical benefit (complete or partial response, confirmed or unconfirmed, or stable disease ≥ 24 weeks) and overall survival of patients treated with these regimens. * Compare adverse events in patients treated with these regimens. * Determine the prognostic significance of estrogen receptor positivity and HER2/neu status in patients treated with these regimens. * Determine parameters of estrogen and clinical pharmacology and estrogen levels in patients treated with these regimens. * Compare anastrozole plasma levels at 8, 16, and 24 weeks in patients treated with these regimens (closed as of 4/16/2009). * Compare estradiol serum levels at 8, 16, and 24 weeks in patients treated with these regimens (closed as of 4/16/2009). OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant tamoxifen therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral anastrozole once daily on days 1-28. * Arm II: Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed for up to 4 years. PROJECTED ACCRUAL: A total of 690 patients (345 per treatment arm) will be accrued for this study within 3 years.
Interventions
DRUGanastrozole
Given orally
DRUGfulvestrant
Given intramuscularly
Sponsors
National Cancer Institute (NCI)
NCIC Clinical Trials Group
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer meeting 1 of the following criteria: * Metastatic disease (M1) * Multiple sites of new disease that is clinically obvious metastatic disease (e.g., multiple sites of new osseous disease) * Measurable or nonmeasurable disease * No known brain or CNS metastases * Hormone receptor status: * Estrogen-receptor positive\* AND/OR * Progesterone-receptor positive\* NOTE: \*Positivity defined as estrogen binding of \> 10 fmol/mg cytosol protein by ligand binding assay or positive by immunohistochemistry PATIENT CHARACTERISTICS: Age * Not specified Sex * Female Menopausal status * Postmenopausal, as defined by 1 of the following: * Prior bilateral oophorectomy * More than 12 months since last menstrual period with no prior hysterectomy * At least 55 years of age with prior hysterectomy * Under 55 years of age with a prior hysterectomy without oophorectomy and with estradiol and follicle-stimulating hormone levels consistent with menopause Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * No bleeding diathesis (e.g., disseminated intravascular coagulation or clotting factor deficiency) Hepatic * INR ≤ 1.6 Renal * Not specified Other * HIV negative * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy * No prior immunotherapy for recurrent or metastatic disease Chemotherapy * No prior chemotherapy for recurrent or metastatic disease * More than 12 months since prior adjuvant or neoadjuvant chemotherapy * No concurrent chemotherapy for malignancy Endocrine therapy * Prior adjuvant hormonal therapy allowed * At least 12 months since prior adjuvant luteinizing hormone-releasing hormone (LHRH) analogues * Menstrual periods must not have resumed since LHRH therapy * More than 12 months since prior adjuvant or neoadjuvant aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane) * More than 12 months since prior fulvestrant * No prior hormonal therapy for recurrent or metastatic disease * No other concurrent hormonal therapy for malignancy * No concurrent hormone replacement therapy Radiotherapy * Not specified Surgery * Not specified Other * No long-term anticoagulant therapy (except antiplatelet therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tumor Progression | Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first. | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. From date of randomization to time of first documentation of progression, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression free are considered at last date of contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks). | Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable, Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Clinical Benefit = CR + PR + Stable \>= 24 weeks |
| Overall Survival | Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first. | From date of randomization to date of death due to any cause. Patients last known to be alive are censored at last date of contact. |
| Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment. | Adverse Events (AEs) are reported by CTCAE version 3.0 terminology. For each patient, worst grade of each event type is reported. Grade3 (Severe), Grade4 (Life-threatening), Grade 5 (Fatal) |
Countries
Canada, United States
Participant flow
Recruitment details
707 Patients underwent randomization. 12 were excluded: 9 did not have metastatic disease, 1 had previous chemotherapy, 1 was estrogen-receptor and progesterone-receptor negative, 1 did not undergo chest imaging. In addition, 1 patient withdrew consent. 694 patients were included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Anastrozole Patients receive oral anastrozole once daily on days 1-28.
anastrozole: Given orally | 345 |
| Arm II Anastrozole and Fulvestrant Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses.
anastrozole: Given orally
fulvestrant: Given intramuscularly | 349 |
| Total | 694 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 12 |
| Overall Study | Death | 4 | 8 |
| Overall Study | Delinquent | 4 | 2 |
| Overall Study | Not protocol specified | 27 | 19 |
| Overall Study | Progression | 269 | 274 |
| Overall Study | Still on treatment | 8 | 15 |
| Overall Study | Under review | 0 | 1 |
| Overall Study | Withdrawal by Subject | 28 | 18 |
Baseline characteristics
| Characteristic | Arm I Anastrozole | Total | Arm II Anastrozole and Fulvestrant |
|---|---|---|---|
| Age, Continuous | 65 years | 65 years | 65 years |
| Disease site Bone only | 76 participants | 151 participants | 75 participants |
| Disease site Nonvisceral | 102 participants | 195 participants | 93 participants |
| Disease site Visceral | 167 participants | 348 participants | 181 participants |
| HER2 status Negative | 270 participants | 536 participants | 266 participants |
| HER2 status Positive | 25 participants | 56 participants | 31 participants |
| Measurable disease No | 157 participants | 318 participants | 161 participants |
| Measurable disease Yes | 188 participants | 376 participants | 188 participants |
| Prior adjuvant chemotherapy No | 242 participants | 462 participants | 220 participants |
| Prior adjuvant chemotherapy Yes | 103 participants | 232 participants | 129 participants |
| Prior adjuvant tamoxifen No | 206 participants | 414 participants | 208 participants |
| Prior adjuvant tamoxifen Yes | 139 participants | 280 participants | 141 participants |
| Sex: Female, Male Female | 345 Participants | 694 Participants | 349 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Time between diagnosis of primary and metastatic disease >= 10 yr | 88 participants | 192 participants | 104 participants |
| Time between diagnosis of primary and metastatic disease 3 mo to < 5 yr | 40 participants | 87 participants | 47 participants |
| Time between diagnosis of primary and metastatic disease 5 to < 10 yr | 68 participants | 134 participants | 66 participants |
| Time between diagnosis of primary and metastatic disease None | 141 participants | 263 participants | 122 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 309 / 337 | 322 / 348 |
| serious Total, serious adverse events | 21 / 337 | 48 / 348 |
Outcome results
Primary
Time to Tumor Progression
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. From date of randomization to time of first documentation of progression, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression free are considered at last date of contact.
Time frame: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I Anastrozole | Time to Tumor Progression | 13.5 months |
| Arm II Anastrozole and Fulvestrant | Time to Tumor Progression | 15.0 months |
p-value: 0.00795% CI: [0.68, 0.94]Log Rank
Secondary
Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks).
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable, Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Clinical Benefit = CR + PR + Stable \>= 24 weeks
Time frame: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I Anastrozole | Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks). | 70 percentage of participants |
| Arm II Anastrozole and Fulvestrant | Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks). | 73 percentage of participants |
Secondary
Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE version 3.0 terminology. For each patient, worst grade of each event type is reported. Grade3 (Severe), Grade4 (Life-threatening), Grade 5 (Fatal)
Time frame: Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment.
Population: Eligible patients who had received the protocol treatments were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mood alteration - agitation | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema: limb | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mood alteration - anxiety | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Albumin, serum-low (hypoalbuminemia) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mood alteration - depression | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue (asthenia, lethargy, malaise) | 7 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis/stomatitis (functional/symp) - Pharynx | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Calcium, serum-high (hypercalcemia) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness, not d/t neuropathy - body/general | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 3 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neurology-Other (Specify) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fracture | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neuropathy: sensory | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cataract | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophils/granulocytes (ANC/AGC) | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Glucose, serum-high (hyperglycemia) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Abdomen NOS | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Back | 5 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hemoglobin | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Bone | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Breast | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hemolysis | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Buttock | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Chest/thorax NOS | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Chest wall | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Extremity-limb | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hot flashes/flushes | 2 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Head/headache | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Joint | 5 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 2 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Muscle | 3 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Neck | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Pelvis | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain-Other (Specify) | 2 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelets | 2 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | AST, SGOT | 3 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash/desquamation | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infection with unknown ANC - Urinary tract NOS | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sodium, serum-low (hyponatremia) | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Speech impairment (e.g., dysphasia or aphasia) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sudden death | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bilirubin (hyperbilirubinemia) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope (fainting) | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint-effusion | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombosis/embolism (vascular access-related) | 3 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombosis/thrombus/embolism | 6 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytes (total WBC) | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tinnitus | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tumor flare | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphopenia | 3 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urticaria (hives, welts, wheals) | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea (shortness of breath) | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 3 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Memory impairment | 1 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 0 Participants |
| Arm I Anastrozole | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CNS cerebrovascular ischemia | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight gain | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Chest/thorax NOS | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | AST, SGOT | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Albumin, serum-low (hypoalbuminemia) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Alkaline phosphatase | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CNS cerebrovascular ischemia | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Calcium, serum-high (hypercalcemia) | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Cataract | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Confusion | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dizziness | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea (shortness of breath) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Edema: limb | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue (asthenia, lethargy, malaise) | 9 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Febrile neutropenia | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fracture | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Glucose, serum-high (hyperglycemia) | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hemoglobin | 3 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hemolysis | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hot flashes/flushes | 7 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Infection with unknown ANC - Urinary tract NOS | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Insomnia | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Joint-effusion | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Leukocytes (total WBC) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphopenia | 3 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Memory impairment | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mood alteration - agitation | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mood alteration - anxiety | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mood alteration - depression | 3 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis/stomatitis (functional/symp) - Pharynx | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Muscle weakness, not d/t neuropathy - body/general | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neurology-Other (Specify) | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neuropathy: sensory | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophils/granulocytes (ANC/AGC) | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Abdomen NOS | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Back | 7 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Bone | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Breast | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Buttock | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Extremity-limb | 3 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Head/headache | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Joint | 7 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Muscle | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Neck | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Pelvis | 3 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain-Other (Specify) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelets | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash/desquamation | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sodium, serum-low (hyponatremia) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Speech impairment (e.g., dysphasia or aphasia) | 0 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sudden death | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope (fainting) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombosis/embolism (vascular access-related) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thrombosis/thrombus/embolism | 7 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tinnitus | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Tumor flare | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urticaria (hives, welts, wheals) | 1 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 2 Participants |
| Arm II Anastrozole and Fulvestrant | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pain - Chest wall | 1 Participants |
Secondary
Overall Survival
From date of randomization to date of death due to any cause. Patients last known to be alive are censored at last date of contact.
Time frame: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I Anastrozole | Overall Survival | 41.3 months |
| Arm II Anastrozole and Fulvestrant | Overall Survival | 47.7 months |
p-value: 0.04995% CI: [0.65, 1]Log Rank