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NCT00066573 · CITED IN SOURCE DOCUMENTS

Exemestane or Anastrozole in Treating Postmenopausal Women Who Have Undergone Surgery for Primary 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
2023-08-25

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy, using exemestane or anastrozole, may fight breast cancer by reducing the production of estrogen. It is not yet known whether exemestane is more effective than anastrozole in preventing the recurrence of breast cancer. PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared to anastrozole in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary 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

Event-free Survival

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outcome · POSTED

Overall Survival: Percentage of Participants Alive at 5 Years

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outcome · POSTED

Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence

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outcome · POSTED

Clinical Fracture Rate: Number of Participants With Bone Fractures.

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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 invasive breast cancer * pT1-3; pNX, pN0-2 or pN3\*; M0 * Neoadjuvant patients are eligible no earlier than 3 weeks or later than 3 months after excisional surgery, provided both the clinical-diagnostic staging of cancer and postsurgical resection-pathologic staging of cancer meet the requirements for primary tumor, regional lymph nodes, and distant metastasis classification NOTE: \*Only when the sole basis for this classification is the presence of 10 or more involved axillary lymph nodes * Completely resected disease * Primary surgery performed at least 3 weeks but no more than 3 months before study entry (if no chemotherapy was given) * Primary surgery is defined as the last surgery at which histologic evidence of invasive or in situ disease was present in the pathology specimen * Patients with positive sentinel lymph node biopsy are eligible provided they have had a subsequent axillary lymph node dissection * No metachronous breast cancer * Bilateral mammogram within the past 12 months unless initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required * No metastases confirmed by 1 of the following methods: * Bone scan\* (required only if alkaline phosphatase is at least 2 times normal and/or there are symptoms of metastatic disease) * Abdominal ultrasound or CT scan (required only if AST/ALT or alkaline phosphatase is at least 2 times normal, unless the elevation is in the bone fraction) * Chest x-ray NOTE: \*Confirmatory x-ray, CT scan, or MRI required if the bone scan results are questionable * No locally recurrent disease * No prior or concurrent carcinoma in situ of the contralateral breast treated with partial mastectomy and/or hormonal therapy * Patients with prior or concurrent carcinoma in situ of the ipsilateral breast are eligible provided the tumor was completely excised AND they have not received prior hormonal therapy * Hormone receptor status: * Estrogen receptor- and/or progesterone receptor-positive by immunohistochemistry or tumor receptor content ≥ 10 fmol/mg protein PATIENT CHARACTERISTICS: Age * Postmenopausal Sex * Female Menopausal status * Postmenopausal prior to chemotherapy, defined as 1 of the following: * Over 60 years of age * Age 45-59 with spontaneous cessation of menses for more than 1 year prior to study entry * Age 45-59 with menses ceasing (secondary to hysterectomy or spontaneously) within the past year AND a follicle-stimulating hormone (FSH) level prior to study entry in the postmenopausal range\* * Age 45-59, previously on hormone replacement therapy (HRT) and have discontinued HRT upon diagnosis of this malignancy AND has an FSH level prior to study entry in the postmenopausal range\* * Has undergone bilateral oophorectomy NOTE: \*By institutional standards OR \> 34.4 IU/L if institutional range is not available) Performance status * ECOG 0-2 Life expectancy * At least 5 years Hematopoietic * WBC at least 3,000/mm\^3 OR * Granulocyte count at least 1,500/mm\^3 AND * Platelet count at least 100,000/mm\^3 Hepatic * See Disease Characteristics * AST and/or ALT less than 2 times upper limit of normal (ULN)\* * Alkaline phosphatase less than 2 times ULN\* NOTE: \*Unless imaging examinations have ruled out metastatic disease Renal * Not specified Other * Able to swallow study medication and have adequate unassisted oral intake in order to maintain reasonable nutrition status * No other non-breast malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years * No other concurrent medical or psychiatric condition that would preclude study participation and/or interfere with results PRIOR CONCURRENT THERAPY: Biologic therapy * Prior and concurrent trastuzumab (Herceptin®) allowed Chemotherapy * See Disease Characteristics * At least 3 weeks but no more than 3 months since prior chemotherapy * Prior adjuvant chemotherapy allowed Endocrine therapy * See Disease Characteristics * No prior aromatase inhibitor * No prior tamoxifen or other selective estrogen receptor modulators (SERMs) except raloxifene * At least 3 weeks since prior raloxifene * At least 3 weeks since prior and no concurrent over-the-counter products or supplements considered to have an estrogenic effect, including any of the following: * Ginseng * Ginkgo biloba * Black cohosh * Dong quai * Fortified soy supplements (e.g., phytoestrogen preparations) * At least 3 weeks since other prior hormonal therapy or steroids considered to have an estrogenic effect * No concurrent estrogens, progesterones, androgens, or SERMs * Concurrent intermittent vaginal estrogens (e.g., vagifem, estrogen vaginal cream, testosterone, estradiol vaginal gel, or Estring) allowed if other local measures for intractable vaginal atrophy are insufficient * No other concurrent therapy that would have an estrogenic effect, including endocrine therapy, hormonal therapy, or steroid therapy Radiotherapy * See Disease Characteristics * Prior adjuvant radiotherapy allowed * Concurrent radiotherapy allowed Surgery * See Disease Characteristics
healthy Volunteers
false
maximum Age
120 Years
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive oral exemestane (25 mg) once daily for 5 years.
    intervention Names
    1. Drug: exemestane
    label
    Exemestane
    type
    EXPERIMENTAL
  2. description
    Patients receive oral anastrozole (1 mg) once daily for 5 years.
    intervention Names
    1. Drug: anastrozole
    label
    Anastrozole
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Anastrozole
    description
    Given orally
    name
    anastrozole
    type
    DRUG
  2. arm Group Labels
    1. Exemestane
    description
    Given orally
    name
    exemestane
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
QUADRUPLE
who Masked
  1. PARTICIPANT
  2. CARE_PROVIDER
  3. INVESTIGATOR
  4. OUTCOMES_ASSESSOR
primary Purpose
TREATMENT
Enrollment
count
7576
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.
    measure
    Event-free Survival
    time Frame
    5 years
secondary Outcomes
  1. description
    Overall survival is defined as the time from randomization to the time of death from any cause.
    measure
    Overall Survival: Percentage of Participants Alive at 5 Years
    time Frame
    5 years
  2. description
    Time to distant disease-free survival (DDFS) is defined as the time from randomization to the time of documented distant recurrence. Distant recurrence is the cancer coming back in a part of the body away from the breast, such as the bones or liver.
    measure
    Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence
    time Frame
    5 years
  3. description
    Clinical fracture at any time, including hip, spine, wrist fractures and other bone fractures.
    measure
    Clinical Fracture Rate: Number of Participants With Bone Fractures.
    time Frame
    8 years
Full study description
brief Summary
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy, using exemestane or anastrozole, may fight breast cancer by reducing the production of estrogen. It is not yet known whether exemestane is more effective than anastrozole in preventing the recurrence of breast cancer. PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared to anastrozole in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary breast cancer.
detailed Description
OBJECTIVES: Primary * Compare the event-free survival of postmenopausal women with receptor-positive primary breast cancer when treated with exemestane vs anastrozole. Secondary * Compare the overall survival of patients treated with these regimens. * Compare the time to distant recurrence in patients treated with these regimens. * Compare the incidence of new primary contralateral breast cancer in patients treated with these regimens. * Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens. * Compare cardiovascular morbidity and mortality (i.e., significant coronary heart disease, which includes myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths) in patients treated with these regimens. * Correlate therapy induced changes in breast density with plasma hormones and growth factors, drug levels of exemestane and anastrozole, genetic variation and breast cancer recurrence or contralateral events in patients treated with these regimens. * Compare the toxic effects of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and herceptin use (yes vs no). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral exemestane (25 mg) once daily for 5 years. * Arm II: Patients receive oral anastrozole (1 mg) once daily for 5 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months during the first year of study participation and annually thereafter. PROJECTED ACCRUAL: A total of 6,840 patients will be accrued for this study.
Source references
references
  1. citation
    Moy B, Elliott CR, Chapman J-AW, et al.: NCIC CTG MA.27: menopausal symptoms of ethnic minority women. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3059, S144, 2006.
    type
    RESULT
  2. citation
    Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. doi: 10.1200/JCO.2012.44.7805. Epub 2013 Jan 28.
    pmid
    23358971
    type
    RESULT
  3. citation
    Pilgram L, Yang K, Beltran-Bless AA, Pond GR, Vandermeer L, Hilton J, Savard MF, LeBlanc A, Shepherd L, Chen B, Bartlett JM, Taylor KJ, Bayani J, Barker S, Spears M, van der Velde CJ, Meershoek-Klein Kranenbarg E, Dirix L, Mallon E, Hasenburg A, Markopoulos C, Juwara L, Dankar FK, Clemons M, El Emam K. Transfer Learning and Machine Learning for Training Five-Year Survival Prognostic Models in Early Breast Cancer: Development and Validation Study. J Med Internet Res. 2026 Apr 14;28:e88665. doi: 10.2196/88665.
    pmid
    41980703
    type
    DERIVED
  4. citation
    Chapman JW, Bayani J, SenGupta S, Bartlett JMS, Piper T, Quintayo MA, Virk S, Goss PE, Ingle JN, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Gelmon KA, Whelan TJ, Elliott C, Shepherd LE, Chen BE, Taylor KJ. Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole. J Clin Oncol. 2024 Aug 20;42(24):2887-2898. doi: 10.1200/JCO.24.00835. Epub 2024 Jun 2.
    pmid
    38824432
    type
    DERIVED
  5. citation
    Ethier JL, Anderson GM, Austin PC, Clemons M, Parulekar W, Shepherd L, Summers Trasiewicz L, Tu D, Amir E. Influence of the competing risk of death on estimates of disease recurrence in trials of adjuvant endocrine therapy for early-stage breast cancer: A secondary analysis of MA.27, MA.17 and MA.17R. Eur J Cancer. 2021 May;149:117-127. doi: 10.1016/j.ejca.2021.02.034. Epub 2021 Apr 11.
    pmid
    33853037
    type
    DERIVED
  6. citation
    Strasser-Weippl K, Higgins MJ, Chapman JW, Ingle JN, Sledge GW, Budd GT, Ellis MJ, Pritchard KI, Clemons MJ, Badovinac-Crnjevic T, Han L, Gelmon KA, Rabaglio M, Elliott C, Shepherd LE, Goss PE. Effects of Celecoxib and Low-dose Aspirin on Outcomes in Adjuvant Aromatase Inhibitor-Treated Patients: CCTG MA.27. J Natl Cancer Inst. 2018 Sep 1;110(9):1003-1008. doi: 10.1093/jnci/djy017.
    pmid
    29554282
    type
    DERIVED
  7. citation
    Strasser-Weippl K, Sudan G, Ramjeesingh R, Shepherd LE, O'Shaughnessy J, Parulekar WR, Liedke PER, Chen BE, Goss PE. Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27. Eur J Cancer. 2018 Feb;90:19-25. doi: 10.1016/j.ejca.2017.11.014. Epub 2017 Dec 20.
    pmid
    29274617
    type
    DERIVED
  8. citation
    Yerushalmi R, Dong B, Chapman JW, Goss PE, Pollak MN, Burnell MJ, Levine MN, Bramwell VHC, Pritchard KI, Whelan TJ, Ingle JN, Shepherd LE, Parulekar WR, Han L, Ding K, Gelmon KA. Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials. Ann Oncol. 2017 Jul 1;28(7):1560-1568. doi: 10.1093/annonc/mdx152.
    pmid
    28379421
    type
    DERIVED
  9. citation
    Stearns V, Chapman JA, Ma CX, Ellis MJ, Ingle JN, Pritchard KI, Budd GT, Rabaglio M, Sledge GW, Le Maitre A, Kundapur J, Liedke PE, Shepherd LE, Goss PE. Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. J Clin Oncol. 2015 Jan 20;33(3):265-71. doi: 10.1200/JCO.2014.57.6926. Epub 2014 Dec 15.
    pmid
    25512454
    type
    DERIVED
  10. citation
    Goetz MP, Schaid DJ, Wickerham DL, Safgren S, Mushiroda T, Kubo M, Batzler A, Costantino JP, Vogel VG, Paik S, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM, Ingle JN, Ames MM. Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res. 2011 Nov 1;17(21):6944-51. doi: 10.1158/1078-0432.CCR-11-0860. Epub 2011 Aug 31.
    pmid
    21880792
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      1. context
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        display
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    Preserved source evidence · Not medical advice