Metastatic Breast Carcinoma, Stage IIIB Breast Cancer AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7
Conditions
Brief summary
This randomized phase II trial studies how well fulvestrant works with or without bortezomib in treating patients with estrogen receptor positive breast cancer that has spread to other places in the body and cannot be removed by surgery. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Bortezomib may stop the growth of breast cancer cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether fulvestrant is more effective with or without bortezomib in treating breast cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine if the addition of bortezomib to fulvestrant improves median progression free survival (PFS) compared with fulvestrant alone in postmenopausal women with estrogen receptor (ER)-positive locally advanced inoperable or metastatic breast cancer who have disease that is resistant to aromatase inhibitor therapy (Arms A versus \[vs.\] B). SECONDARY OBJECTIVES: I. To determine if the addition of bortezomib to fulvestrant improves the clinical benefit rate (defined as objective response plus stable disease for at least 24 weeks from day +1). II. To determine the percent of patients, treated with fulvestrant alone and fulvestrant plus bortezomib, who remain progression-free 24 weeks from day +1 (Arms A vs. B). III. To determine the overall survival of patients treated with fulvestrant alone and fulvestrant plus bortezomib (Arms A, B, C). IV. To determine the adverse event profile in patients treated with fulvestrant alone and fulvestrant plus bortezomib (Arms A, B, C). V. To determine the clinical benefit rate at 12 and 24 weeks of fulvestrant plus bortezomib in patients who have progressed on the fulvestrant alone arm and crossover to receive the combination (Arm C). TERTIARY OBJECTIVES: I. To perform an exploratory analysis of the effects of bortezomib (plus fulvestrant) in intratumoral nuclear/cytoplasmic ER ratio, unfolded protein response (BiP), apoptosis (cleaved caspase 3), B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (Bcl-2) phospho c-Jun N-terminal kinase (JNK) in patients with tumors accessible to biopsy who consent to optional post-treatment biopsy. II. To determine with cyclin D1 expression in pretreatment tumor specimens (from metastatic disease or the primary tumor if the former is not available) is predictive of clinical benefit with fulvestrant-bortezomib. OUTLINE: Patients are randomized to 1 of 2 treatment arms (Arms A or B). ARM A: Patients receive fulvestrant intramuscularly (IM) on day 1 (days -14, 1, and 15 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may crossover to arm C. ARM B: Patients receive fulvestrant as in arm A and bortezomib intravenously (IV) on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive fulvestrant IM on day 1 and bortezomib IV on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months.
Interventions
DRUGBortezomib
Given IV
DRUGFulvestrant
Given IM
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ELIGIBILITY CRITERIA FOR ARM A AND ARM B * Patients must have histologically or cytologically confirmed ER+ positive breast cancer * Patients must be postmenopausal, defined as: (1) a history of at least 12 months without spontaneous menstrual bleeding, (2) prior bilateral salpingo-oophorectomy, with or without hysterectomy, (3) age \>= 55 years with a prior hysterectomy with or without oophorectomy, (4) age \< 55 years with a prior hysterectomy without oophorectomy or unknown status, with a documented follicle-stimulating hormone (FSH) level in postmenopausal range within 4 week s of registration, (5) receiving a gonadotropin releasing hormone analog (GnRH) to suppress ovarian function (eg, goserelin 3.6 mg every \[q\] 4 weeks) * Patients must have stage IV disease or inoperable locally advanced disease * Patients may have measurable disease only, non-measurable disease only, or both (Response Evaluation Criteria in Solid Tumors \[RECIST 1.1\]); it is anticipated that at least 50% of patients will have only non-measurable disease * Patients are required to have disease that is resistant to aromatase inhibitor (AI), which is defined either as relapse while receiving adjuvant A.I. therapy (ie, anastrazole, letrozole, or exemestane), and/or disease progression after one or more A.I.s for metastatic disease; prior exposure to more than one AI is permitted * Patient may have had prior tamoxifen but are not required to * Patients may have received up to one prior chemotherapy regimen for metastatic disease * Patients may have received prior bevacizumab * Patients who have received up to 2 doses of fulvestrant given within a 4 week period prior to registration are eligible; the interval between the first fulvestrant dose and registration must be 6 weeks or less; patients may have received EITHER 250 mg or 500 mg of fulvestrant previously; if the patient has received 250 mg, they will receive the 500 mg loading dose on study day -14; if they already received 500 mg, they will begin the study on day +1 * Life expectancy of greater than 3 months * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Leukocytes \>= 3,000/mcL * Absolute neutrophil count \>= 1,500/mcL * Platelets \>= 100,000/mcL * Total bilirubin within normal institutional limits * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal * Creatinine within normal institutional limits OR * Creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal * Patients must be disease-free of prior invasive malignancies for \>= 5 years with the exception of: curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix * Patients must have the ability to understand and the willingness to sign a written informed consent document * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * ELIGIBILITY CRITERIA FOR ARM C * Previously met all eligibility criteria for arms A and B and registered on trial to arm A (fulvestrant alone) * Disease progression on arm A and agreeable to crossover to arm C * Has received no intervening therapy (ie, alternative endocrine therapy, chemotherapy, biologic therapy) between disease progression on arm A and registration an arm C * ECOG performance status 0-2 * Tumor measurements (eg, computed tomography \[CT\] scan of chest/abdomen/pelvis) within 4 weeks of registration to arm C * Leukocytes \>= 3,000/mcL, within 2 weeks of registration on arm C * Absolute neutrophil count \>= 1,500/mcL, within 2 weeks of registration on arm C * Platelets \>= 100,000/mcL, within 2 weeks of registration on arm C * Total bilirubin within normal institutional limits, within 2 weeks of registration on arm C * AST(SGOT)/ALT(SGPT) =\< 2.5 x institutional upper limit of normal, within 2 weeks of registration on arm C * Creatinine within normal institutional limits, within 2 weeks of registration on arm C OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal, within 2 weeks of registration on arm C
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression Free Survival (PFS) at 12 Months | At 12 months | The number of patients, treated with fulvestrant alone and fulvestrant plus bortezomib, who remained progression-free (Arms A vs. B). 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 lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Number of Participants With Progression Free Survival (PFS) at 6 Months | At 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) of Adding Bortezomib to Fulvestrant in Arm C | Up to 24 weeks | This outcome measure determined if the addition of bortezomib to fulvestrant improved the clinical benefit rate (defined as objective response plus stable disease for at least 24 weeks from day+1). Clinical Benefit Rate (CBR) is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents. |
| Number of Participants Who Survived Until Study End (up to 7 Years) | From first treatment day until study end, assessed up to 7 years | Tabulation of the number of participants who survived from the date of first treatment until study end (up to 7 years). |
| Progression Free Survival at 24 Weeks (Arm C) | At 24 weeks | — |
| Frequency of Most Common Toxicities | Up to 7 years | Most common toxicities in the fulvestrant arm alone (Arm A) and the fulvestrant/bortezomib combination arm (Arm B). Most common toxicities are defined as adverse events having occurred in \>10% of the participants within either (or both) Arm A or Arm B. |
Countries
United States
Participant flow
Recruitment details
118 patients were enrolled from 17 institutions between May 2010 and October 2013
Pre-assignment details
118 postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A) or in combination with bortezomib (Arm B). Two patients randomized to Arm B never received protocol therapy. Of 59 patients randomized to fulvestrant alone, Arm A, 27 crossed over to receive fulvestrant plus bortezomib (Arm C) at progression on fulvestrant alone.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Fulvestrant Patients received fulvestrant IM on day 1 (days -14, 1, and 15 of course 1 only). Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may crossover to Arm C.
Fulvestrant: Given IM
Laboratory Biomarker Analysis: Correlative studies | 59 |
| Arm B: Fulvestrant + Bortezomib Patients received fulvestrant IM as in Arm A and bortezomib IV on days 1, 8, and 15. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity.
Bortezomib: Given IV
Fulvestrant: Given IM
Laboratory Biomarker Analysis: Correlative studies | 57 |
| Total | 116 |
Baseline characteristics
| Characteristic | Arm B: Fulvestrant + Bortezomib | Total | Arm A: Fulvestrant |
|---|---|---|---|
| Age, Continuous | 59 years | 57 years | 57 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 57 participants | 116 participants | 59 participants |
| Sex: Female, Male Female | 57 Participants | 116 Participants | 59 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 59 | 15 / 57 | 9 / 27 |
| other Total, other adverse events | 59 / 59 | 57 / 57 | 27 / 27 |
| serious Total, serious adverse events | 9 / 59 | 6 / 57 | 5 / 27 |
Outcome results
Primary
Number of Participants With Progression Free Survival (PFS) at 12 Months
The number of patients, treated with fulvestrant alone and fulvestrant plus bortezomib, who remained progression-free (Arms A vs. B). 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 lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Fulvestrant | Number of Participants With Progression Free Survival (PFS) at 12 Months | 8 Participants |
| Arm B: Fulvestrant + Bortezomib | Number of Participants With Progression Free Survival (PFS) at 12 Months | 16 Participants |
Primary
Number of Participants With Progression Free Survival (PFS) at 6 Months
Time frame: At 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Fulvestrant | Number of Participants With Progression Free Survival (PFS) at 6 Months | 16 Participants |
| Arm B: Fulvestrant + Bortezomib | Number of Participants With Progression Free Survival (PFS) at 6 Months | 22 Participants |
Secondary
Clinical Benefit Rate (CBR) of Adding Bortezomib to Fulvestrant in Arm C
This outcome measure determined if the addition of bortezomib to fulvestrant improved the clinical benefit rate (defined as objective response plus stable disease for at least 24 weeks from day+1). Clinical Benefit Rate (CBR) is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Time frame: Up to 24 weeks
Population: \# of participants randomized to Arm A (Fulvestrant alone) who crossed over to fulvestrant plus bortezomib at progression (Arm C) and had clinical benefit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Fulvestrant | Clinical Benefit Rate (CBR) of Adding Bortezomib to Fulvestrant in Arm C | 5 Participants |
Secondary
Frequency of Most Common Toxicities
Most common toxicities in the fulvestrant arm alone (Arm A) and the fulvestrant/bortezomib combination arm (Arm B). Most common toxicities are defined as adverse events having occurred in \>10% of the participants within either (or both) Arm A or Arm B.
Time frame: Up to 7 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Dyspnea | 32 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hyponatremia/Sodium-Low | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Cough | 29 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hot Flashes | 37 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Fatigue | 56 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Nausea | 29 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Limb Edema | 19 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | SGOT (AST-High) | 25 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Insomnia | 25 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Dizziness | 7 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Vomiting | 14 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Arthralgia | 36 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | White Blood Cell-Low | 32 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Anxiety | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Diarrhea | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Fever | 15 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | SGPT (ALT-High) | 14 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Pruritis | 7 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Constipation | 34 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Rash/Desquamation | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Myalgia | 10 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Depression | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Heartburn/Dyspepsia | 10 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Anemia | 32 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Neutrophil Count Decreased/ANC-low | 10 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Dry Eye | 0 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Anorexia | 15 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hypertension | 12 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hyperglycemia/Glucose-High | 44 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Rash (General) | 7 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Headache | 12 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Eye Disorders (not otherwise specified) | 7 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Platelet Count Decreased/Platelets-Low | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Urinary Disorders (General) | 15 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Pain (general) | 59 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Thrombocytopenia | 41 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hemoglobin-Low | 41 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Neutropenia | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Peripheral Neuropathy (Motor, Pain, Sensory) | 31 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Upper Respiratory Disorders (General) | 12 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hypocalcemia/Calcium-Low | 10 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Musculoskeletal Pain Disorders (not otherwise specified) | 17 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Injection Site Reaction | 24 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Mucositis Oral | 8 percentage of participants |
| Arm A: Fulvestrant | Frequency of Most Common Toxicities | Hypoglycemia/Glucose-Low | 5 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Mucositis Oral | 11 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hot Flashes | 32 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Arthralgia | 28 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hemoglobin-Low | 61 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | White Blood Cell-Low | 42 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hyperglycemia/Glucose-High | 51 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hypoglycemia/Glucose-Low | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | SGOT (AST-High) | 32 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | SGPT (ALT-High) | 21 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Neutrophil Count Decreased/ANC-low | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Platelet Count Decreased/Platelets-Low | 30 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hypocalcemia/Calcium-Low | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hyponatremia/Sodium-Low | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Nausea | 63 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Vomiting | 32 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Diarrhea | 47 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Constipation | 46 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Heartburn/Dyspepsia | 18 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Anorexia | 23 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Headache | 25 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Pain (general) | 54 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Peripheral Neuropathy (Motor, Pain, Sensory) | 49 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Injection Site Reaction | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Dyspnea | 19 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Cough | 23 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Fatigue | 56 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Limb Edema | 37 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Dizziness | 19 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Myalgia | 18 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Anxiety | 19 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Fever | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Pruritis | 16 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Rash/Desquamation | 11 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Depression | 16 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Anemia | 42 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Dry Eye | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Hypertension | 21 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Rash (General) | 23 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Eye Disorders (not otherwise specified) | 12 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Urinary Disorders (General) | 11 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Thrombocytopenia | 61 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Neutropenia | 30 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Upper Respiratory Disorders (General) | 23 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Musculoskeletal Pain Disorders (not otherwise specified) | 18 percentage of participants |
| Arm B: Fulvestrant + Bortezomib | Frequency of Most Common Toxicities | Insomnia | 35 percentage of participants |
Secondary
Number of Participants Who Survived Until Study End (up to 7 Years)
Tabulation of the number of participants who survived from the date of first treatment until study end (up to 7 years).
Time frame: From first treatment day until study end, assessed up to 7 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Fulvestrant | Number of Participants Who Survived Until Study End (up to 7 Years) | 39 Participants |
| Arm B: Fulvestrant + Bortezomib | Number of Participants Who Survived Until Study End (up to 7 Years) | 42 Participants |
Secondary
Progression Free Survival at 24 Weeks (Arm C)
Time frame: At 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Fulvestrant | Progression Free Survival at 24 Weeks (Arm C) | 5 Participants |