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NCT00075764 · CITED IN SOURCE DOCUMENTS

S0226 Anastrozole With or Without Fulvestrant as First-Line Therapy in Postmenopausal Women With Metastatic Breast Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2021-01-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Time to Tumor Progression

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outcome · POSTED

Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks).

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outcome · POSTED

Overall Survival

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outcome · POSTED

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility 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)
healthy Volunteers
false
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive oral anastrozole once daily on days 1-28.
    intervention Names
    1. Drug: anastrozole
    label
    Arm I
    type
    ACTIVE_COMPARATOR
  2. description
    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.
    intervention Names
    1. Drug: anastrozole
    2. Drug: fulvestrant
    label
    Arm II
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given orally
    name
    anastrozole
    type
    DRUG
  2. arm Group Labels
    1. Arm II
    description
    Given intramuscularly
    name
    fulvestrant
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
695
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Time to Tumor Progression
    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.
secondary Outcomes
  1. description
    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
    measure
    Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 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.
  2. description
    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.
    measure
    Overall Survival
    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.
  3. description
    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)
    measure
    Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
    time Frame
    Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment.
Full study description
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.
Source references
references
  1. citation
    Bergqvist M, Nordmark A, Williams A, Paoletti C, Barlow W, Cobain EF, Mehta RS, Gralow JR, Hortobagyi GN, Albain KS, Pusztai L, Sharma P, Godwin AK, Thompson AM, Hayes DF, Rae JM. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226). Biomarkers. 2023 May;28(3):313-322. doi: 10.1080/1354750X.2023.2168063. Epub 2023 Jan 29.
    pmid
    36647745
    type
    DERIVED
  2. citation
    Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Linden HH, Livingston RB, Hortobagyi GN. Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer. N Engl J Med. 2019 Mar 28;380(13):1226-1234. doi: 10.1056/NEJMoa1811714.
    pmid
    30917258
    type
    DERIVED
  3. citation
    Unger JM, LeBlanc M, Blanke CD. The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population. JAMA Oncol. 2017 Oct 1;3(10):1345-1351. doi: 10.1001/jamaoncol.2017.0762.
    pmid
    28586789
    type
    DERIVED
  4. citation
    Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. doi: 10.1056/NEJMoa1201622.
    pmid
    22853014
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      occurrences
      1. context exact
        vidence (combination endocrine therapy with an AI and fulvestrant):</p> <div class="pdq-content-list"><ol id="_2211"><li>The <a href="/clinicaltrials/NCT00075764">SWOG-0226</a> trial (NCT00075764), which enrolled 707 patients, demonstrated a statistically significant difference in PFS (HR, 0.80; 95% CI, 0.68&#8211;0.94;
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      2. context exact
        rapy with an AI and fulvestrant):</p> <div class="pdq-content-list"><ol id="_2211"><li>The <a href="/clinicaltrials/NCT00075764">SWOG-0226</a> trial (NCT00075764), which enrolled 707 patients, demonstrated a statistically significant difference in PFS (HR, 0.80; 95% CI, 0.68&#8211;0.94; <em>P</em> = .007) and OS (HR, 0.
        end
        596089
        exact text
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        start
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      2026-09-09T23:21:35.419733+00:00
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      source title
      Breast Cancer Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 25, 2025
        datetime
        2025-04-25T12:00:00Z
        display
        April 25, 2025

    Preserved source evidence · Not medical advice